References for BBQ or Smoke Meat?
Benzpyrene aka Benzopyrene, Benzyprene, BP
A toxic Polynuclear Aromatic Hydrocarbon formed as a result of Food Processing involving heat.
Toxic effects:
- May cause Lung Cancer
- May cause Liver damage
- May cause Emphysema
- May cause depletion of Vitamin A; esp from the lungs and liver
Sources of:
- Motor vehicle exhausts
- Frying or overheating of dietary oils [food processing]
- Barbequing, frying, and smoking of meats [food processing]
- Tobacco smoke
Food that may counteract:
- Coffee may detoxify from body
- Blueberries, Raspberries, and Strawberries may inhibit the carcinogenic potential of
- Black Cumin may inhibit cell mutations by
- Korean Ginseng may prevent liver damage from
- Peppermint (real, not candy) may prevent Lung Cancer from
- Kombu, a Japanese kelp, may remove from the body
Other Substances that may counteract:
- Vitamins C and E may prevent the conversion to carcinogens
- Quercetin may block damage to DNA and inhibit ability to cause cancer
- D-Glucaric Acid may block the cancer causing ability
=== === ===
· Edes, T. E., et al. Carcinogen-induced tissue vitamin A depletion. Potential protective advantages of beta-carotene. Ann N Y Acad Sci. 686:203-211, 1993.
Department of Internal Medicine, Harry S. Truman Memorial Veterans Affairs Hospital, Columbia, Missouri.
Exposure to benzopyrene, an enzyme-inducing PAH carcinogen, promotes vitamin A depletion in exposed tissues. This effect is evident while on a vitamin A sufficient diet and without a decline in serum retinol. The finding of local tissue vitamin depletion without systemic depletion may have considerable implications in maintaining tissue health. While the described studies involved dietary exposure to benzopyrene, it is reasonable to extrapolate that inhalation exposure via cigarette smoke would have a similar effect in the lungs and perhaps stomach and bladder. Higher MFO enzyme activity in the lungs may have detrimental effects. Kellermann's early work identifying a higher incidence of lung cancer in those with genetically greater aryl hydrocarbon hydroxylase activity was interpreted as due to the greater formation of a reactive intermediate in the process of carcinogen metabolism. As an alternative hypothesis the author suggests that those with higher enzyme inducibility may have greater carcinogen-induced vitamin A depletion. If poor tissue vitamin A nutriture potentiates the carcinogenicity of compounds such as benzopyrene, dietary or pharmacologic interventions which improve tissue nutriture could be important. The demonstrated effect of dietary beta-carotene on preventing carcinogen-induced tissue vitamin A depletion suggests one mechanism by which beta-carotene may be cancer protective. Further investigations are warranted, particularly with inhalation exposure to carcinogens and the effect of dietary beta-carotene on lung tissue nutriture.
===
· Steinkellner, H., et al. Coffee consumption induces GSTP in plasma and protects lymphocytes against (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-
epoxide induced DNA-damage: results of controlled human intervention trials. Mutat Res. 2005.
Institute of Cancer Research, Medical University of Vienna, Vienna, Austria.
A number of animal studies indicate that coffee protects against chemical induction of cancer; also human studies suggest that coffee consumption is inversely related with the incidence of different forms of cancer. The protective effects were attributed to induction of glutathione
-S-transferases (GSTs) and aim of the present human study was to find out if coffee causes induction of GSTs and protects against DNA-damage caused by (+/-)-anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), the DNA-reactive metabolite of benzo(a)pyrene. Ten participants consumed 1L unfiltered coffee/d over 5 days. Before and after the intervention, saliva and blood were collected and the overall GST activity was measured with 1-chloro-2,4-dinitrobenzene (CDNB). Additionally, GSTP and GSTA were determined in plasma with immunoassays. In blood, only weak (p=0.042) induction of GST (CDNB) was found. Furthermore, pronounced (three-fold) induction of GSTP was observed in blood, whereas GSTA was not altered. No correlations were seen between induction of GST (CDNB) and GSTP activities and the GSTP1 genotypes of the participants. Also clinical parameters (creatinine, alanine, aminotransferase, aspartate aminotransferase, alkaline phosphatase), which are markers for organ damage, were monitored. None of them was altered by coffee, but serum cholesterol levels were slightly (not significantly) enhanced. In a second trial (n=7), GSTP induction by unfiltered and paper filtered coffees, differing in cafestol and kahweol contents, were compared. The participants consumed 1L coffee/d over 3 days. Again significant (three-fold) induction of GSTP was observed. The effects seen with the two coffees were identical, indicating that the diterpenoid concentrations are not responsible for the effects. In a further trial (n=7), the effect of coffee (unfiltered, 1L/d, 5 days) on BPDE induced DNA-migration was studied in comet assays. A 45% reduction effect was observed. These findings show that coffee induces GSTP in humans and indicate that consumption may lead to protection towards polycyclic aromatic hydrocarbons.
===
· Hope Smith, S., et al. Antimutagenic activity of berry extracts. J Med Food. 7(4):450-455, 2004.
Department of Microbiology, Clemson University, Clemson, South Carolina, USA.
Plants are proven sources of useful anti-tumor and chemopreventative compounds. Hence, identification of phytochemicals useful in dietary prevention and intervention of cancer is of paramount importance. The initial step in the formation of cancer is damage to the genome of a somatic cell producing a mutation in an oncogene or a tumor-suppressor gene. Fresh juices and organic solvent extracts from the fruits of strawberry, blueberry, and raspberry were evaluated for their ability to inhibit the production of mutations by the direct-acting mutagen methyl methanesulfonate and the metabolically activated carcinogen benzo[a]pyrene. Juice from strawberry, blueberry, and raspberry fruit significantly inhibited mutagenesis caused by both carcinogens. Ethanol extracts from freeze-dried fruits of strawberry cultivars (Sweet Charlie and Carlsbad) and blueberry cultivars (Tifblue and Premier) were also tested. Of these, the hydrolyzable tannin-containing fraction from Sweet Charlie strawberries was most effective at inhibiting mutations.
===
· Badary, O. A., et al. Anticlastogenic activity of thymoquinone against benzo(a)pyrene in mice. Food Chem Toxicol. 45(1):88-92, 2007.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Helwan, Cairo, Egypt.
Thymoquione (TQ), the main constituent of the volatile oil of Nigella sativa seeds, has been shown to protect mice against benzo(a)pyrene [B(a)P]-induced forestomach carcinogenesis. The present investigation was undertaken to study the possible chemopreventive activity of TQ, supplemented in the drinking water, against B(a)P-induced chromosomal aberrations (CAs) in mouse bone marrow cells. Male Swiss albino mice received TQ (0.01% in drinking water) daily for 28 days. The daily dose of TQ was estimated to be 10mg/kg based on the calculated average daily water consumption by mice. From day 9, the carcinogen, B(a)P, was given by gastric intubation at dose level of 50mg/kg on alternative days for a total of 8 doses. On day 29, all mice were transferred to a normal drinking tap water. Control groups received corn oil vehicle, TQ alone or B(a)P alone. All mice were sacrificed at 12 weeks after the end of the treatment. Chromosome preparations were made of bone marrow. Cytogenetic end points screened were the frequencies of CAs and damaged cells induced. Daily intake of TQ after and before or during exposure to B(a)P significantly reduced the frequencies of CAs and damaged cells compared to the highly clastogenic activity of B(a)P alone.
===
· Gum, S. I., et al. The potent protective effect of wild ginseng (Panax ginseng C.A. Meyer) against benzo[alpha]pyrene-induced toxicity through metabolic regulation of CYP1A1 and GSTs. Journal of Ethnopharmacology. 2007.
College of Oriental Medicine and Research Institute of Oriental Medicine, Dongguk University, Kyungju, Republic of Korea.
Wild Panax ginseng C.A. Meyer (WG) is a well-known medicinal herb. In this study, the protective effects of a water extract from the root of WG on benzo[alpha]pyrene (BP)-induced hepatotoxicity and the mechanism of these effects were investigated for the first time. The effects of WG on liver toxicities induced by BP were assessed by blood biochemical and histopathological analyses. BP caused severe liver injury in rats, as indicated by elevated plasma ALT, AST and LPO levels. Pretreatment with WG for 4 weeks completely abrogated increases in the ALT, AST and LPO levels when challenged with BP. Reductions in GSH content and GST activity by BP were reversed by WG. These protective effects of WG against BP-induced toxicity were consistent with the results of histopathological examinations. The authors then examined the effects of WG on the gene expression of the enzymes that metabolize BP in H4IIE cells. CYP1A1 mRNA and protein expression were increased by BP. WG moderately inhibited BP-induced CYP1A1 gene expression. Moreover, GSTA2, GSTA3 and GSTM2 gene expressions were significantly increased by WG through the Nrf2/antioxidant responsive element pathway for enzyme induction. WG is efficacious in protecting against BP-induced hepatotoxicity as results of metabolic regulations through both the inhibition of metabolic enzyme activation and the enhancement of electrophilic detoxification, implying that WG should be considered a potential chemopreventive agent.
===
· Smarth, R. M., et al. Modulatory effects of Mentha piperita on lung tumor incidence, genotoxicity, and oxidative stress in benzo[a]pyrene-treated Swiss albino mice. Environ Mol Mutagen. 2005.
Radiation and Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur, India.
Mentha piperita or peppermint is currently used for alleviating nausea, flatulence, and vomiting. In the present investigation, the authors evaluated the chemopreventive, antigenotoxic, and antioxidative effects of an aqueous extract of Mentha piperita leaves. One-day-old Swiss albino mice were treated with a single subcutaneous injection of 0.5 mg benzo[a]pyrene (BP) and then given either water or a Mentha extract (ME; 1 g/kg body weight) by gavage starting at 3 weeks of age (weaning). The mice were killed at 9 weeks of age and tested for lung tumor incidence (chemoprevention); bone marrow micronucleus and chromosome aberration frequency (antigenotoxicity); and levels of liver and lung sulfhydral groups, superoxide dismutase (SOD) and catalase (CAT) activity, and lipid peroxidation (LPO) (antioxidative properties). The ME treatment resulted in a significant reduction in the number of lung adenomas from an incidence of 67.92% in animals given only BP to 26.31%, an inhibition of 61.26%. Tumor multiplicity was 1.22 in the BP-alone group and 1.15 in the BP + ME group. In addition, compared with the animals in the BP-alone group, ME reduced the frequency of chromosomal aberrations and micronuclei in bone marrow cells and decreased the levels of LPO and increased reduced glutathione content, and SOD and CAT activities in liver as well as lung. The results of this study indicate that ME is chemopreventive and antigenotoxic when given subsequent to an initiating dose of BP in newborn Swiss albino mice. The chemopreventive action and antigenotoxic effects observed in the present study may be due to the antioxidative properties of ME.
· Smarth, R. M., et al. Protective effects of Mentha piperita Linn on benzo[a]pyrene-induced lung carcinogenicity and mutagenicity in Swiss albino mice. Mutagenesis. 2006.
Radiation and Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur, India.
The chemopreventive and antimutagenic effects of an aqueous extract of Mentha piperita leaves were evaluated by using 9 week medium term model of benzo[a]pyrene (BP)-induced lung tumors. Lung tumors were induced by a single subcutaneous injection in the scapular region with BP in newborn Swiss albino mice (<24 h old). The oral administration of Mentha extract (ME) showed a significant reduction in the number of lung tumors from an incidence of 67.92% in animals given only BP to 26.31%. The inhibition rate was 61.26% in ME treated group with respect to reference group (BP-alone). However, tumor multiplicity was reduced from 0.83 in the BP-alone group to 0.31 in the BP + ME group. Also, ME treatment reduced the frequency of BP-induced chromosomal aberrations and micronuclei in bone marrow cells and decreased the levels of lipoperoxides and increased sulfhydryl groups in liver as well as lung. In cell-free assays, ME showed strong scavenging activity for both the DPPH(*) and ABTS(*+) radicals. ME had an IC50 value of 272 microg/ml in the DPPH(*) assay. The chemopreventive action and antimutagenic effects observed in the present study is attributed to the antioxidative and radical scavenging properties of ME.
===
· Sakakibara, H., et al. Effects of Japanese kelp (kombu) on life span of benzo[a]pyrene-fed mice. J Nutr Sci Vitaminol (Tokyo). 51(5):369-373, 2005.
Department of Life Science, Graduate School of Science and Technology, Kobe University, Rokkodai, Nada-ku, Kobe, Japan.
The prolonging effect of Japanese kelp (kombu) on life span was investigated in mice fed a diet containing the carcinogen benzo[a]pyrene (BaP). Three groups of six mice each were fed a normal diet with 0, 2 and 5%, kombu powder, while another three groups were fed those diets with 4 ppm BaP loading. The 2 and 5% kombu diets did not affect life span compared to the control group given 0%, kombu. BaP significantly reduced the life span. Addition of 2 or 5%, kombu to the BaP diet remarkably recovered the life span to a level similar to that of the control. The feces of the 2 and 5% kombu groups contained 6.9+/-1.2 and 16.8+/-1.8% of the ingested BaP, respectively, mainly in forms adsorbed on kombu fibers. The BaP-alone group given cellulose as dietary fiber instead of kombu, did not show any such effects. Humans are exposed to various environmental carcinogens such as BaP, and kombu fibers probably contribute to longevity by removing them.
===
· Gajecka, M., et al. The protective effect of vitamins C and E against B(a)P-induced genotoxicity in human lymphocytes. J Environ Pathol Toxicol Oncol. 18(3):159-167, 1999.
Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Polycyclic aromatic hydrocarbons (PAH) are a well-characterized group of mutagens and carcinogens. Benzo(a)pyrene [B(a)P], the best known compound in the group, exerts its genotoxic activity following metabolic activation, when it acquires the properties of an electrophilic reagent that is capable of interacting with DNA. Reactive oxygen species (ROS) can remerge during the PAH metabolic activation. Because of their antioxidant activity, vitamins C and E are thought to act as antimutagenic agents. The authors designed an in vitro protocol to study the potential protective effect of vitamins C and E toward B(a)P-induced DNA damage. The authors examined peripheral blood lymphocytes obtained from healthy nonsmoking female volunteers, 22 to 25 years of age. The cells were exposed in vitro to 1 microM B(a)P in the presence of 40 microM or 100 microM of vitamin C or, alternatively, to 30 microM or 100 microM of vitamin E. The B(a)P-induced DNA damage and repair were estimated as the generation and removal of single-strand DNA breaks measured by the alkaline version of the single-cell gel electrophoresis (comet) assay. The protective effect of vitamins C and E was demonstrated when the vitamins were applied simultaneously with or after the B(a)P. The background level of DNA damage in the presence of vitamins C and E was lower than in the system without the vitamins. The experiments were conducted according to various protocol schemes of the vitamin treatment and the results offer additional evidence of the antigenotoxic activity of vitamins C and E. The vitamin activity does not appear to be connected with the steps in metabolic activation or DNA repair. It appears that both vitamins act as competitors of DNA molecule in reaction with the reactive oxygen species.
===
· Jin, N. Z., et al. Preventive effects of quercetin against benzo[a]pyrene-induced DNA damages and pulmonary precancerous pathologic changes in mice. Basic Clin Pharmacol Toxicol. 98(6):593-598, 2006.
Institute of Toxicology, Nanjing Medical University, Nanjing, China.
The aim of this study was to investigate the preventive effects of quercetin against benzo[a]pyrene-induced blood lymphocyte DNA damages and pulmonary precancerous pathologic changes in mice, and to reveal the potential mechanism behind these effects. In this study, mice in quercetin-treated groups were given quercetin for 90 days. After one week of treatment, mice in the quercetin-treated groups and the positive control group received a single intraperitoneal dose of benzo[a]pyrene (100 mg/kg body weight). The results of single cell gel electrophoresis assay showed that the average lengths of the comet cell tail and DNA damage in the peripheral blood lymphocytes of mice induced by benzo[a]pyrene decreased significantly as a result of quercetin treatment dose-dependently. Light microscopic examination showed that the degrees of pulmonary precancerous pathologic changes in the quercetin-treated groups decreased significantly compared with those in the positive control group. Meanwhile, the cytochrome P4501A1-linked 7-ethoxyresorufin O-dealkylase activities in lung microsomes of mice decreased as the dose of quercetin increased. The results of this in vivo study revealed that quercetin had a significant preventive effect on benzo[a]pyrene-induced DNA damage, and had a potential chemopreventive effect on the carcinogenesis of lung cancer induced by benzo[a]pyrene. The mechanism of these effects of quercetin could be related to the inhibition of cytochrome P4501A1 activity.
===
· Walaszek, Z., et al. Dietary glucarate-mediated reduction of sensitivity of murine strains to chemical carcinogenesis. Cancer Letters. 33(1):25-32, 1986.
When mice were exposed to carcinogens from tobacco smoke that are known to initiate lung cancer, D-glucaric acid was found to inhibit the development of lung cancer. D-glucaric acid caused a 70% reduction in the binding of benzopyrene to DNA in mouse lungs.
· Walaszek, Z., et al. Potential use of D-glucaric acid derivatives in cancer prevention. Cancer Letters. 54(1-2):1-8, 1990.
Primary source: In-Tele-Health © 2008 (from Hyperhealth Pro CD-ROM)
A toxic Polynuclear Aromatic Hydrocarbon formed as a result of Food Processing involving heat.
Toxic effects:
- May cause Lung Cancer
- May cause Liver damage
- May cause Emphysema
- May cause depletion of Vitamin A; esp from the lungs and liver
Sources of:
- Motor vehicle exhausts
- Frying or overheating of dietary oils [food processing]
- Barbequing, frying, and smoking of meats [food processing]
- Tobacco smoke
Food that may counteract:
- Coffee may detoxify from body
- Blueberries, Raspberries, and Strawberries may inhibit the carcinogenic potential of
- Black Cumin may inhibit cell mutations by
- Korean Ginseng may prevent liver damage from
- Peppermint (real, not candy) may prevent Lung Cancer from
- Kombu, a Japanese kelp, may remove from the body
Other Substances that may counteract:
- Vitamins C and E may prevent the conversion to carcinogens
- Quercetin may block damage to DNA and inhibit ability to cause cancer
- D-Glucaric Acid may block the cancer causing ability
=== === ===
· Edes, T. E., et al. Carcinogen-induced tissue vitamin A depletion. Potential protective advantages of beta-carotene. Ann N Y Acad Sci. 686:203-211, 1993.
Department of Internal Medicine, Harry S. Truman Memorial Veterans Affairs Hospital, Columbia, Missouri.
Exposure to benzopyrene, an enzyme-inducing PAH carcinogen, promotes vitamin A depletion in exposed tissues. This effect is evident while on a vitamin A sufficient diet and without a decline in serum retinol. The finding of local tissue vitamin depletion without systemic depletion may have considerable implications in maintaining tissue health. While the described studies involved dietary exposure to benzopyrene, it is reasonable to extrapolate that inhalation exposure via cigarette smoke would have a similar effect in the lungs and perhaps stomach and bladder. Higher MFO enzyme activity in the lungs may have detrimental effects. Kellermann's early work identifying a higher incidence of lung cancer in those with genetically greater aryl hydrocarbon hydroxylase activity was interpreted as due to the greater formation of a reactive intermediate in the process of carcinogen metabolism. As an alternative hypothesis the author suggests that those with higher enzyme inducibility may have greater carcinogen-induced vitamin A depletion. If poor tissue vitamin A nutriture potentiates the carcinogenicity of compounds such as benzopyrene, dietary or pharmacologic interventions which improve tissue nutriture could be important. The demonstrated effect of dietary beta-carotene on preventing carcinogen-induced tissue vitamin A depletion suggests one mechanism by which beta-carotene may be cancer protective. Further investigations are warranted, particularly with inhalation exposure to carcinogens and the effect of dietary beta-carotene on lung tissue nutriture.
===
· Steinkellner, H., et al. Coffee consumption induces GSTP in plasma and protects lymphocytes against (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-
epoxide induced DNA-damage: results of controlled human intervention trials. Mutat Res. 2005.
Institute of Cancer Research, Medical University of Vienna, Vienna, Austria.
A number of animal studies indicate that coffee protects against chemical induction of cancer; also human studies suggest that coffee consumption is inversely related with the incidence of different forms of cancer. The protective effects were attributed to induction of glutathione
-S-transferases (GSTs) and aim of the present human study was to find out if coffee causes induction of GSTs and protects against DNA-damage caused by (+/-)-anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), the DNA-reactive metabolite of benzo(a)pyrene. Ten participants consumed 1L unfiltered coffee/d over 5 days. Before and after the intervention, saliva and blood were collected and the overall GST activity was measured with 1-chloro-2,4-dinitrobenzene (CDNB). Additionally, GSTP and GSTA were determined in plasma with immunoassays. In blood, only weak (p=0.042) induction of GST (CDNB) was found. Furthermore, pronounced (three-fold) induction of GSTP was observed in blood, whereas GSTA was not altered. No correlations were seen between induction of GST (CDNB) and GSTP activities and the GSTP1 genotypes of the participants. Also clinical parameters (creatinine, alanine, aminotransferase, aspartate aminotransferase, alkaline phosphatase), which are markers for organ damage, were monitored. None of them was altered by coffee, but serum cholesterol levels were slightly (not significantly) enhanced. In a second trial (n=7), GSTP induction by unfiltered and paper filtered coffees, differing in cafestol and kahweol contents, were compared. The participants consumed 1L coffee/d over 3 days. Again significant (three-fold) induction of GSTP was observed. The effects seen with the two coffees were identical, indicating that the diterpenoid concentrations are not responsible for the effects. In a further trial (n=7), the effect of coffee (unfiltered, 1L/d, 5 days) on BPDE induced DNA-migration was studied in comet assays. A 45% reduction effect was observed. These findings show that coffee induces GSTP in humans and indicate that consumption may lead to protection towards polycyclic aromatic hydrocarbons.
===
· Hope Smith, S., et al. Antimutagenic activity of berry extracts. J Med Food. 7(4):450-455, 2004.
Department of Microbiology, Clemson University, Clemson, South Carolina, USA.
Plants are proven sources of useful anti-tumor and chemopreventative compounds. Hence, identification of phytochemicals useful in dietary prevention and intervention of cancer is of paramount importance. The initial step in the formation of cancer is damage to the genome of a somatic cell producing a mutation in an oncogene or a tumor-suppressor gene. Fresh juices and organic solvent extracts from the fruits of strawberry, blueberry, and raspberry were evaluated for their ability to inhibit the production of mutations by the direct-acting mutagen methyl methanesulfonate and the metabolically activated carcinogen benzo[a]pyrene. Juice from strawberry, blueberry, and raspberry fruit significantly inhibited mutagenesis caused by both carcinogens. Ethanol extracts from freeze-dried fruits of strawberry cultivars (Sweet Charlie and Carlsbad) and blueberry cultivars (Tifblue and Premier) were also tested. Of these, the hydrolyzable tannin-containing fraction from Sweet Charlie strawberries was most effective at inhibiting mutations.
===
· Badary, O. A., et al. Anticlastogenic activity of thymoquinone against benzo(a)pyrene in mice. Food Chem Toxicol. 45(1):88-92, 2007.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Helwan, Cairo, Egypt.
Thymoquione (TQ), the main constituent of the volatile oil of Nigella sativa seeds, has been shown to protect mice against benzo(a)pyrene [B(a)P]-induced forestomach carcinogenesis. The present investigation was undertaken to study the possible chemopreventive activity of TQ, supplemented in the drinking water, against B(a)P-induced chromosomal aberrations (CAs) in mouse bone marrow cells. Male Swiss albino mice received TQ (0.01% in drinking water) daily for 28 days. The daily dose of TQ was estimated to be 10mg/kg based on the calculated average daily water consumption by mice. From day 9, the carcinogen, B(a)P, was given by gastric intubation at dose level of 50mg/kg on alternative days for a total of 8 doses. On day 29, all mice were transferred to a normal drinking tap water. Control groups received corn oil vehicle, TQ alone or B(a)P alone. All mice were sacrificed at 12 weeks after the end of the treatment. Chromosome preparations were made of bone marrow. Cytogenetic end points screened were the frequencies of CAs and damaged cells induced. Daily intake of TQ after and before or during exposure to B(a)P significantly reduced the frequencies of CAs and damaged cells compared to the highly clastogenic activity of B(a)P alone.
===
· Gum, S. I., et al. The potent protective effect of wild ginseng (Panax ginseng C.A. Meyer) against benzo[alpha]pyrene-induced toxicity through metabolic regulation of CYP1A1 and GSTs. Journal of Ethnopharmacology. 2007.
College of Oriental Medicine and Research Institute of Oriental Medicine, Dongguk University, Kyungju, Republic of Korea.
Wild Panax ginseng C.A. Meyer (WG) is a well-known medicinal herb. In this study, the protective effects of a water extract from the root of WG on benzo[alpha]pyrene (BP)-induced hepatotoxicity and the mechanism of these effects were investigated for the first time. The effects of WG on liver toxicities induced by BP were assessed by blood biochemical and histopathological analyses. BP caused severe liver injury in rats, as indicated by elevated plasma ALT, AST and LPO levels. Pretreatment with WG for 4 weeks completely abrogated increases in the ALT, AST and LPO levels when challenged with BP. Reductions in GSH content and GST activity by BP were reversed by WG. These protective effects of WG against BP-induced toxicity were consistent with the results of histopathological examinations. The authors then examined the effects of WG on the gene expression of the enzymes that metabolize BP in H4IIE cells. CYP1A1 mRNA and protein expression were increased by BP. WG moderately inhibited BP-induced CYP1A1 gene expression. Moreover, GSTA2, GSTA3 and GSTM2 gene expressions were significantly increased by WG through the Nrf2/antioxidant responsive element pathway for enzyme induction. WG is efficacious in protecting against BP-induced hepatotoxicity as results of metabolic regulations through both the inhibition of metabolic enzyme activation and the enhancement of electrophilic detoxification, implying that WG should be considered a potential chemopreventive agent.
===
· Smarth, R. M., et al. Modulatory effects of Mentha piperita on lung tumor incidence, genotoxicity, and oxidative stress in benzo[a]pyrene-treated Swiss albino mice. Environ Mol Mutagen. 2005.
Radiation and Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur, India.
Mentha piperita or peppermint is currently used for alleviating nausea, flatulence, and vomiting. In the present investigation, the authors evaluated the chemopreventive, antigenotoxic, and antioxidative effects of an aqueous extract of Mentha piperita leaves. One-day-old Swiss albino mice were treated with a single subcutaneous injection of 0.5 mg benzo[a]pyrene (BP) and then given either water or a Mentha extract (ME; 1 g/kg body weight) by gavage starting at 3 weeks of age (weaning). The mice were killed at 9 weeks of age and tested for lung tumor incidence (chemoprevention); bone marrow micronucleus and chromosome aberration frequency (antigenotoxicity); and levels of liver and lung sulfhydral groups, superoxide dismutase (SOD) and catalase (CAT) activity, and lipid peroxidation (LPO) (antioxidative properties). The ME treatment resulted in a significant reduction in the number of lung adenomas from an incidence of 67.92% in animals given only BP to 26.31%, an inhibition of 61.26%. Tumor multiplicity was 1.22 in the BP-alone group and 1.15 in the BP + ME group. In addition, compared with the animals in the BP-alone group, ME reduced the frequency of chromosomal aberrations and micronuclei in bone marrow cells and decreased the levels of LPO and increased reduced glutathione content, and SOD and CAT activities in liver as well as lung. The results of this study indicate that ME is chemopreventive and antigenotoxic when given subsequent to an initiating dose of BP in newborn Swiss albino mice. The chemopreventive action and antigenotoxic effects observed in the present study may be due to the antioxidative properties of ME.
· Smarth, R. M., et al. Protective effects of Mentha piperita Linn on benzo[a]pyrene-induced lung carcinogenicity and mutagenicity in Swiss albino mice. Mutagenesis. 2006.
Radiation and Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur, India.
The chemopreventive and antimutagenic effects of an aqueous extract of Mentha piperita leaves were evaluated by using 9 week medium term model of benzo[a]pyrene (BP)-induced lung tumors. Lung tumors were induced by a single subcutaneous injection in the scapular region with BP in newborn Swiss albino mice (<24 h old). The oral administration of Mentha extract (ME) showed a significant reduction in the number of lung tumors from an incidence of 67.92% in animals given only BP to 26.31%. The inhibition rate was 61.26% in ME treated group with respect to reference group (BP-alone). However, tumor multiplicity was reduced from 0.83 in the BP-alone group to 0.31 in the BP + ME group. Also, ME treatment reduced the frequency of BP-induced chromosomal aberrations and micronuclei in bone marrow cells and decreased the levels of lipoperoxides and increased sulfhydryl groups in liver as well as lung. In cell-free assays, ME showed strong scavenging activity for both the DPPH(*) and ABTS(*+) radicals. ME had an IC50 value of 272 microg/ml in the DPPH(*) assay. The chemopreventive action and antimutagenic effects observed in the present study is attributed to the antioxidative and radical scavenging properties of ME.
===
· Sakakibara, H., et al. Effects of Japanese kelp (kombu) on life span of benzo[a]pyrene-fed mice. J Nutr Sci Vitaminol (Tokyo). 51(5):369-373, 2005.
Department of Life Science, Graduate School of Science and Technology, Kobe University, Rokkodai, Nada-ku, Kobe, Japan.
The prolonging effect of Japanese kelp (kombu) on life span was investigated in mice fed a diet containing the carcinogen benzo[a]pyrene (BaP). Three groups of six mice each were fed a normal diet with 0, 2 and 5%, kombu powder, while another three groups were fed those diets with 4 ppm BaP loading. The 2 and 5% kombu diets did not affect life span compared to the control group given 0%, kombu. BaP significantly reduced the life span. Addition of 2 or 5%, kombu to the BaP diet remarkably recovered the life span to a level similar to that of the control. The feces of the 2 and 5% kombu groups contained 6.9+/-1.2 and 16.8+/-1.8% of the ingested BaP, respectively, mainly in forms adsorbed on kombu fibers. The BaP-alone group given cellulose as dietary fiber instead of kombu, did not show any such effects. Humans are exposed to various environmental carcinogens such as BaP, and kombu fibers probably contribute to longevity by removing them.
===
· Gajecka, M., et al. The protective effect of vitamins C and E against B(a)P-induced genotoxicity in human lymphocytes. J Environ Pathol Toxicol Oncol. 18(3):159-167, 1999.
Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Polycyclic aromatic hydrocarbons (PAH) are a well-characterized group of mutagens and carcinogens. Benzo(a)pyrene [B(a)P], the best known compound in the group, exerts its genotoxic activity following metabolic activation, when it acquires the properties of an electrophilic reagent that is capable of interacting with DNA. Reactive oxygen species (ROS) can remerge during the PAH metabolic activation. Because of their antioxidant activity, vitamins C and E are thought to act as antimutagenic agents. The authors designed an in vitro protocol to study the potential protective effect of vitamins C and E toward B(a)P-induced DNA damage. The authors examined peripheral blood lymphocytes obtained from healthy nonsmoking female volunteers, 22 to 25 years of age. The cells were exposed in vitro to 1 microM B(a)P in the presence of 40 microM or 100 microM of vitamin C or, alternatively, to 30 microM or 100 microM of vitamin E. The B(a)P-induced DNA damage and repair were estimated as the generation and removal of single-strand DNA breaks measured by the alkaline version of the single-cell gel electrophoresis (comet) assay. The protective effect of vitamins C and E was demonstrated when the vitamins were applied simultaneously with or after the B(a)P. The background level of DNA damage in the presence of vitamins C and E was lower than in the system without the vitamins. The experiments were conducted according to various protocol schemes of the vitamin treatment and the results offer additional evidence of the antigenotoxic activity of vitamins C and E. The vitamin activity does not appear to be connected with the steps in metabolic activation or DNA repair. It appears that both vitamins act as competitors of DNA molecule in reaction with the reactive oxygen species.
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· Jin, N. Z., et al. Preventive effects of quercetin against benzo[a]pyrene-induced DNA damages and pulmonary precancerous pathologic changes in mice. Basic Clin Pharmacol Toxicol. 98(6):593-598, 2006.
Institute of Toxicology, Nanjing Medical University, Nanjing, China.
The aim of this study was to investigate the preventive effects of quercetin against benzo[a]pyrene-induced blood lymphocyte DNA damages and pulmonary precancerous pathologic changes in mice, and to reveal the potential mechanism behind these effects. In this study, mice in quercetin-treated groups were given quercetin for 90 days. After one week of treatment, mice in the quercetin-treated groups and the positive control group received a single intraperitoneal dose of benzo[a]pyrene (100 mg/kg body weight). The results of single cell gel electrophoresis assay showed that the average lengths of the comet cell tail and DNA damage in the peripheral blood lymphocytes of mice induced by benzo[a]pyrene decreased significantly as a result of quercetin treatment dose-dependently. Light microscopic examination showed that the degrees of pulmonary precancerous pathologic changes in the quercetin-treated groups decreased significantly compared with those in the positive control group. Meanwhile, the cytochrome P4501A1-linked 7-ethoxyresorufin O-dealkylase activities in lung microsomes of mice decreased as the dose of quercetin increased. The results of this in vivo study revealed that quercetin had a significant preventive effect on benzo[a]pyrene-induced DNA damage, and had a potential chemopreventive effect on the carcinogenesis of lung cancer induced by benzo[a]pyrene. The mechanism of these effects of quercetin could be related to the inhibition of cytochrome P4501A1 activity.
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· Walaszek, Z., et al. Dietary glucarate-mediated reduction of sensitivity of murine strains to chemical carcinogenesis. Cancer Letters. 33(1):25-32, 1986.
When mice were exposed to carcinogens from tobacco smoke that are known to initiate lung cancer, D-glucaric acid was found to inhibit the development of lung cancer. D-glucaric acid caused a 70% reduction in the binding of benzopyrene to DNA in mouse lungs.
· Walaszek, Z., et al. Potential use of D-glucaric acid derivatives in cancer prevention. Cancer Letters. 54(1-2):1-8, 1990.
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