Protective activity of different hepatic cytosolic glutathione S-transferases against DNA-binding metabolites of aflatoxin B1

Quinn, B.A.; Crane, T.L.; Kocal, T. E.; Best, Susan J.; Cameron, Ross; Rushmore, Thomas H.; Farber, Emmanuel; Hayes, Michael

doi:10.1016/0041-008x(90)90139-l

Cited by 51 publications

(16 citation statements)

References 37 publications

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“…For example, in prospective epidemiological studies in southern China using urinary biomarkers of aflatoxin exposure, a 12-fold higher relative risk of liver cancer was observed in HBsAg carriers with detectable urinary aflatoxin metabolites compared to carriers without urinary metabolites (36,40). While these molecular epidemiological studies support an apparent interaction between viral and chemical factors in hepatocarcinogenesis, the underlying molecular mechanisms are unclear.…”

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confidence: 99%

Overexpression of Cytochrome P-450 Isoforms Involved in Aflatoxin B1 Bioactivation in Human Liver with Cirrhosis and Hepatitis

et al. 1996

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Studies were carried out to test the hypothesis that inflammatory liver disease increases the expression of specific cytochrome P-450 isoenzymes involved in aflatoxin B 1 (AFB) activation. The immunohistochemical expression and localization of various human cytochrome P-450 isoforms, including CYP2A6, CYP1A2, CYP3A4, and CYP2B1, were examined in normal human liver and liver with hepatitis and cirrhosis. The constitutive expression of CYP3A4 in normal liver showed a characteristic pattern of distribution in centrilobular hepatocytes, whereas CYP1A2, CYP2A6, and CYP2B1 1 were expressed uniformly throughout the liver acinus. In sections of liver infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), the expression of CYP2A6 was markedly increased in hepatocytes immediately adjacent to areas of fibrosis and inflammation. CYP3A4 and CYP2B 1 were induced to a lesser degree, and expression of CYP1A2 was unaffected. In HBV-infected liver, double immunostaining revealed that overexpression of CYP2A6 occurred in hepatocytes expressing the HBV core antigen. In HCV-infected liver, CYP2A6, CYP3A4, and CYP2B 1 were overexpressed in hepatocytes with hemosiderin pigmentation. These results suggest that alterations in phenotypic expression of specific P-450 isoenzymes in hepatocytes associated with hepatic inflammation and cirrhosis might increase susceptibility to AFB genotoxicity.

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Overexpression of Cytochrome P-450 Isoforms Involved in Aflatoxin B1 Bioactivation in Human Liver with Cirrhosis and Hepatitis

et al. 1996

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“…3,9 The active metabolite AFB 1 -8,9-epoxide is deactivated primarily by GST. Quinn et al 10 reported that hepatic GST activity determines the natural sensitivity of a species or individual Table 5. Testicular glutathione S-transferase (GST) activity a in rats exposed to aflatoxin B 1 to AFB 1 -carcinogenesis rather than the DNA-binding metabolites of AFB 1 .…”

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confidence: 99%

Effects of intermittent exposures of aflatoxin B1 on hepatic and testicular glutathione S‐transferase in rats

et al. 2000

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Glutathione S-transferase (GST) plays a major role in the detoxification of the potent hepatocarcinogen aflatoxin B 1 (AFB 1 ). This study evaluated the effects of intermittent exposures to AFB 1 on hepatic and testicular GST in rats. Male Fischer 344 rats were fed diets containing AFB 1 (0, 0.01, 0.04, 0.4 and 1.6 ppm) intermittently at 4-week intervals up to 20 weeks. The control animals were fed an AFB 1 -free NIH-31 diet. Rats consuming diets with 0.01 ppm AFB 1 did not show the induction of hepatic or testicular GST activity. Intermittent exposures to AFB 1 at concentrations of 0.04-1.6 ppm significantly increased the GST activities. The increase of the enzyme activity was proportional to the dose and length of AFB 1 exposure.

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“…(17J8) In hepatitis B transgenic mice, the development of hepatocellular carcinoma is believed to follow predominantly from liver cell necrosis and associated hepatocellular regeneraThere is evidence that exposure to aflatoxin produces DNA adducts. (21,22) Thus, cell mutation rates are likely to increase with aflatoxin dose. There is little information to indicate whether or not aflatoxin also promotes liver cancer directly by stimulating the growth of initiated cells.…”

Section: Evidence For Mechanism Of Actionmentioning

confidence: 99%

“…The authors discussed some alternatives for modeling the interaction and demonstrated that several alternatives provided adequate statistical fit of the data. Best estimates of aflatoxin potency (in the U.S.) based on a multiplicative relative risk and an interactive excess risk model were 2.6 and 66 vs. 22 and 301 (mgfkg/day)-l for HBsAg-and HBsAg+ populations, respectively. Other alternative models were discussed by Hoseyni.…”

Section: Risk Modelingmentioning

confidence: 99%

Risk Assessment for Aflatoxin: An Evaluation Based on the Multistage Model

et al. 1993

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Lifetime cancer potency of aflatoxin was assessed based on the Yeh et al. study from China in which both aflatoxin exposure and hepatitis B prevalence were measured. This study provides the best available information for estimating the carcinogenic risk posed by aflatoxin to the U.S. population. Cancer potency of aflatoxin was estimated using a biologically motivated risk assessment model. The best estimate of aflatoxin potency was 9 (mg/kg/day)-1 for individuals negative for hepatitis B and 230 (mg/kg/day)-1 for individuals positive for hepatitis B.

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Protective activity of different hepatic cytosolic glutathione S-transferases against DNA-binding metabolites of aflatoxin B1

Cited by 51 publications

References 37 publications

Overexpression of Cytochrome P-450 Isoforms Involved in Aflatoxin B1 Bioactivation in Human Liver with Cirrhosis and Hepatitis

Overexpression of Cytochrome P-450 Isoforms Involved in Aflatoxin B1 Bioactivation in Human Liver with Cirrhosis and Hepatitis

Effects of intermittent exposures of aflatoxin B1 on hepatic and testicular glutathione S‐transferase in rats

Risk Assessment for Aflatoxin: An Evaluation Based on the Multistage Model

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