Modulation of c-myc gene expression in rat livers by aflatoxin B1 exposure and age.
A single dose of aflatoxin B1 (AFB1) caused a rapid and transient induction in c-myc mRNA levels in livers derived from adult male Fischer 344 rats. The inducibility of c-myc expression by AFB1 increased with age as c-myc mRNA levels from untreated livers declined from 18-fold in 29-day-old animals to 1-fold in 39-day-old animals, relative to untreated 43-day-old control animals. A dose-dependent increase in c-myc mRNA was found when 53- and 76-day-old rats were administered various AFB1 doses whereas 29-day-old animals exhibited essentially no change in c-myc mRNA levels for the doses examined. Rats were treated with multiple doses of AFB1 to induce hepatocellular carcinomas. C-myc mRNA levels were measured in rat liver samples taken during and subsequent to chronic AFB1 exposure. Characterization of the c-myc induction response at the time of AFB1 exposure revealed that a transient elevation of c-myc mRNA occurred during each (5-day) dosing period for the first 3 weeks, consistent with the acute exposure studies. RNA prepared from hepatocellular carcinomas exhibited elevated levels of c-myc mRNA compared to vehicle-treated control animals. Examination of tumors isolated from the 28-day-old animals showed that the increased c-myc mRNA observed was not the result of gene amplification or gene rearrangement. A comparison of tumor data showed that the 28-day-old animals had a 100% liver tumor incidence while the 38-day-old rats had a 20% liver tumor incidence.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
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Larson
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McMahon
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Wogan
D016604:Aflatoxin B1 / Q000494:pharmacology*; D000375:Aging / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D016604:Aflatoxin B1