Liver DNA adducts in methyl-deficient rats administered a single dose of aflatoxin B1
| العنوان: | Liver DNA adducts in methyl-deficient rats administered a single dose of aflatoxin B1 |
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| المؤلفون: | Robert Stapley, Edmund McMullen, Rekha Mefata, Gary W. Laver |
| المصدر: | Carcinogenesis. 13:1241-1247 |
| بيانات النشر: | Oxford University Press (OUP), 1992. |
| سنة النشر: | 1992 |
| مصطلحات موضوعية: | Male, Cancer Research, medicine.medical_specialty, Pathology, Aflatoxin B1, DNA Repair, DNA damage, Biology, chemistry.chemical_compound, Methionine, Oral administration, Internal medicine, Acetylaminofluorene, DNA adduct, medicine, Animals, Aspartate Aminotransferases, Biotransformation, Analysis of Variance, Liver Neoplasms, Alanine Transaminase, DNA, General Medicine, 2-Acetylaminofluorene, Rats, Inbred F344, Liver regeneration, Choline Deficiency, Diet, Liver Regeneration, Rats, Regimen, Endocrinology, Liver, chemistry, Alanine transaminase, biology.protein, Precancerous Conditions |
| الوصف: | Using an 8 week Solt-Farber protocol with selection pressure (2-acetylaminofluorene/partial hepatectomy) applied during weeks 6 and 7, we have observed that a single oral administration of aflatoxin B1 (AFB1) to Fischer 344 rats on day 1 of the study, followed by a 3 week feeding regimen of either a methyl-deficient (CMD) or a basal (CMS) diet, results in a relative increase in hepatic preneoplastic lesions in CMD diet fed rats. It has previously been shown that a multiple dosing regimen with AFB1, started after 3 weeks of CMD diet, enhances tumor incidence. In the present study, the role of metabolic activation in the induction of preneoplastic lesions, and liver DNA adduct levels after the first dose of AFB1 in the tumorigenesis model have been investigated. AFB1-DNA adducts were determined at 2-168 h following a single non-necrogenic (100 micrograms/kg body wt) or necrogenic (600 micrograms/kg body wt) dose of AFB1 on day 1 or day 21 of a 3 week treatment with a complete basal or CMD diet. In all rats irrespective of dose, dietary treatment or time of AFB1 dosing, the patterns of adduct formation and repair did not change. In rats receiving AFB1 on day 1, total DNA adduct levels between the diet or dose groups were not significantly different, and quantitatively did not correlate with the observed increase in preneoplastic lesions, suggesting a contribution by additional factors in the initiation of these lesions. Administration of AFB1 on day 21, however, resulted in significantly reduced levels of total adducts at both dose levels in CMD diet fed rats compared to controls. Serum biochemistry data suggest that a prolonged exposure to CMD diet may cause pathological and/or biochemical alterations in hepatocytes with a resultant decrease in metabolic activation of AFB1, thus making it difficult to evaluate whether DNA damage is directly related to tumorigenesis. |
| تدمد: | 1460-2180 0143-3334 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c81e02150247196264645dd76577c3e https://doi.org/10.1093/carcin/13.7.1241 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8c81e02150247196264645dd76577c3e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602180 01433334 |
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