Species-specific differences in hepatic mutant frequency and mutational spectrum among lambda/lacl transgenic rats and mice following exposure to aflatoxin B1

Dycaico, Mark J.; Stuart, Gregory R.; Tobal, G; deBoer, Johan G.; Glickman, B.W.; Provost, Gabrielle S. Le

doi:10.1016/s0928-4346(97)89840-4

Cited by 13 publications

(22 citation statements)

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“…The doses of AF and Vit E used in this study were selected according to previous studies in which Vit E was administered together with AF. [13][14][15][16] The animals were randomly divided into 4 experimental groups including 7 rats in each. These groups were arranged as follows: control group, Vit E group (Vit E was administered), AFB 1 group (a single dose of AFB 1 was administered), AF + Vit E group (AF and Vit E were administered).…”

Section: Experimental Groups and Sample Collectionmentioning

confidence: 99%

Vitamin E (α tocopherol) attenuates toxicity and oxidative stress induced by aflatoxin in rats

Yılmaz¹,

Kaya²,

Çomaklı³

2017

Adv Clin Exp Med

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Section: Experimental Groups and Sample Collectionmentioning

confidence: 99%

Vitamin E (α tocopherol) attenuates toxicity and oxidative stress induced by aflatoxin in rats

Yılmaz¹,

Kaya²,

Çomaklı³

2017

Adv Clin Exp Med

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“…Furthermore, the above-mentioned mutation research was all done in mice, while the present study was conducted in rats. Spontaneous mutation frequencies in the liver of recently developed transgenic rats are substantially lower than those of the transgenic mice similarly developed, and mutation patterns induced by aflatoxin B 1 are clearly different in these two animals Dycaico et al, 1996). It is thus apparent that the mutating events, either spontaneous or induced, are speciesdependent, but the available data for species other than mice are thus far limited.…”

Section: Nakae Et Almentioning

confidence: 99%

“…It is thus apparent that the mutating events, either spontaneous or induced, are speciesdependent, but the available data for species other than mice are thus far limited. In addition, GC-to-AT transitions are the most frequent class among spontaneous mutations Dycaico et al, 1996;Gossen and Vijg, 1993;Kohler et al, 1991;Martus et al, 1995;Vijg et al, 1997;Vijg and van Steeg, 1998), while 8-OHdG specifically induces GC-to-TA transversions (Cheng et al, 1992;Kamiya et al, 1992;Moriya et al, 1991;Shibutani et al, 1991). Different forms of oxidative DNA damage, however, can induce different types of mutations, including transitions, deletions, and frameshifts (Gille et al, 1994;Hsie et al, 1986;Jackson et al, 1998, Kreutzer andEssigman, 1998).…”

Section: Nakae Et Almentioning

confidence: 99%

Age and Organ Dependent Spontaneous Generation of Nuclear 8-Hydroxydeoxyguanosine in Male Fischer 344 Rats

Nakae

Akai

Kishida

et al. 2000

Laboratory Investigation

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SUMMARY: 8-Hydroxydeoxyguanosine (8-OHdG) is a major oxidative DNA adduct playing roles in senescence, carcinogenesis and various disease processes. High-performance liquid chromatography with an electrochemical detection (HPLC-ECD) method has been widely used to assess organ levels of 8-OHdG, and a recently introduced immunohistochemical approach has made it possible to clarify intra-organ localization. In the present study, these methods were employed to reveal age-dependent changes in nuclear 8-OHdG within various tissues of male Fischer 344 rats between 18 fetal days and 104 weeks of age. 8-OHdG was detected in the nuclei of cerebellar small granule and small cortical cells, cerebral nerve cells, and choroid plexus epithelia of the brain and ependymal cells of the spinal cord; parenchymal cells in the anterior lobe of the pituitary and adrenal glands (mainly cortex); bronchial epithelium of the lung; intra-hepatic bile duct, pancreatic duct, glandular gastric and intestinal epithelial cells; renal tubular epithelial cells (mainly medulla); and spermatogonia and spermatocytes of the testis and seminal vesicle epithelia. The nuclear 8-OHdG levels were high (more than two lesions per 10 6 deoxyguanosines) from 7 days to 104 weeks of age in the brain, 3 to 6 weeks in the adrenal gland, 6 to 104 weeks in the lung, and 3 to 52 weeks in the testis. In the other organs, the nuclear 8-OHdG levels remained low throughout. These findings provide a basis for research dealing with oxidative stress by indicating organ-specific and age-but not aging-dependent changes in the localization of spontaneously generated nuclear 8-OHdG in intact rats. The immunohistochemical approach has advantages for assessing variation of 8-OHdG formation at the cellular level not accessible to the HPLC-ECD method. (Lab Invest 2000, 80:249-261).

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“…Mice are naturally resistant to the effects of aflatoxins, presumably due to high levels of reduced glutathione, which reacts with and eliminates the epoxide isoform of AFB1 (12,16,51). To circumvent this innate resistance, male ATX and WT mice were treated with AFB1 when very young (22).…”

mentioning

confidence: 99%

“…The AFB1 carcinogen is activated by the cytochrome P450 monooxygenase system to an active AFB1-8,9-epoxide, which binds covalently to DNA, RNA, and proteins (18). If not repaired by the NER pathway, the primary DNA adduct, 8,9-dihydro-8-(N 7 -guanyl)9-hydroxy-AFB1 (AFB1-N 7 -Gua), predominately causes transversion (purine to pyrimidine or pyrimidine to purine) mutations (1,12,30). As HBx is reported to bind to the UV-damaged DNA binding protein (DDB1 [also known as UV-DDB]) component of NER, mutant cII plaques from ATX and WT mice were isolated and sequenced, to determine whether the interaction between HBx and DDB1 might influence the specific type of DNA mutation formed (28,47,48).…”

mentioning

confidence: 99%

Altered DNA Mutation Spectrum in Aflatoxin B1-Treated Transgenic Mice That Express the Hepatitis B Virus X Protein

Madden¹,

Finegold

Slagle³

2002

J Virol

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Humans chronically infected with hepatitis B virus (HBV) are at further risk of liver cancer upon exposure to dietary aflatoxin B1 (AFB1), a carcinogenic product of the mold Aspergillus flavus. For the present study, we utilized double-transgenic mice (ATX mice) that express the HBV X protein (HBx) and possess a bacteriophage lambda transgene to evaluate the in vivo effect of HBx expression on AFB1-induced DNA mutations. The expression of HBx correlated with a 24% increase in mutation frequency overall and an approximately twofold increase in the incidence of G/C-to-T/A transversion mutations following AFB1 exposure. These results are consistent with a model in which expression of HBx during chronic HBV infection may contribute to the development of hepatocellular carcinoma following exposure to environmental carcinogens.Chronic infection with hepatitis B virus (HBV) is a primary risk factor for the development of hepatocellular carcinoma (HCC) (2, 49). Additional risk factors include chemical agents, such as aflatoxin and ethanol, which can result in liver damage upon repeated exposure (7,56,58). Epidemiological data, as well as experimental studies utilizing transgenic animals, have indicated that chronic HBV infection and exposure to hepatocarcinogens act synergistically in the development of HCC (10,14,31,33,46,50,53,57). However, the mechanism by which chronic HBV infection sensitizes an individual to carcinogeninduced liver cancer remains unknown.The 17-kDa HBV X protein (HBx) is a nonstructural protein necessary for the establishment of hepadnaviral infection in woodchucks and presumably in all mammals (8, 59). Depending upon experimental conditions, HBx is reported to inhibit nucleotide excision repair (NER) (3,17,21,32,41), to influence apoptosis (11,23,39,40,52,54,55), and to induce cell cycle progression (4,26,27). By affecting these pathways, HBx could facilitate the mutagenic effects of hepatocarcinogens or promote the survival and proliferation of hepatocytes altered after exposure. Although transgenic mice that express HBx are more sensitive to the carcinogenic effects of the hepatocarcinogen diethylnitrosamine (DEN [10,33,50]), they do not demonstrate significant increases in overall mutation accumulation (32, 33). These results suggest that HBx contributes to DEN-mediated carcinogenesis by a mechanism that does not involve a dramatic inhibition of DNA repair. Recently, a study demonstrated that expression of HBx increased mutagenesis in a human liver cell line treated with aflatoxin B1 (AFB1) (17). The effect of HBx on AFB1-induced damage in vivo has not been examined.Aflatoxins are a family of potent hepatocarcinogens produced by the mold Aspergillus flavus. A common dietary contaminant in many parts of the world, aflatoxins are metabolized in vivo by cytochrome P450 isoenzymes to form mutagenic epoxides (13). The induction of P450 enzyme levels may explain the increased AFB1 sensitivity of mice that overexpress the hepatitis B surface antigen (24). However, the levels of carcinogen-metabolizin...

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Species-specific differences in hepatic mutant frequency and mutational spectrum among lambda/lacl transgenic rats and mice following exposure to aflatoxin B1

Cited by 13 publications

References 0 publications

Vitamin E (α tocopherol) attenuates toxicity and oxidative stress induced by aflatoxin in rats

Vitamin E (α tocopherol) attenuates toxicity and oxidative stress induced by aflatoxin in rats

Age and Organ Dependent Spontaneous Generation of Nuclear 8-Hydroxydeoxyguanosine in Male Fischer 344 Rats

Altered DNA Mutation Spectrum in Aflatoxin B1-Treated Transgenic Mice That Express the Hepatitis B Virus X Protein

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