Altered expression of retrovirus-like sequences and cellular oncogenes in mice fed methyl-deficient diets.
Methyl-deficient (lipotrope-deficient) diets enhance liver carcinogenesis in rodents. Although the mechanisms responsible for the cancer-promoting activity of such diets have not been identified, they have been observed to cause impaired immune response, alterations in methylation of liver RNA and DNA, and enhanced susceptibility to oxidative damage. Since alterations in gene expression may also play a critical role, the present studies examined the expression of the c-myc, c-H-ras, epidermal growth factor receptor, and ornithine decarboxylase genes, as well as endogenous retrovirus-like sequences, in C57BL/6J x C3H/HeJ F1 mouse liver during the first 2 weeks of feeding of a methyl-deficient diet. The kinetics of liver cell proliferation was investigated in parallel. Increased [3H]thymidine incorporation into liver DNA was found at day 4 and reached a maximum at days 7-11 after commencement of the methyl-deficient diet, when compared to age-matched mice fed a complete diet. Northern blot analysis of polyadenylated liver RNA samples indicated an increase in the levels of RNA homologous to Moloney murine leukemia virus and intracisternal A particle sequences but no significant change in the level of VL30 retrovirus-related RNA in the samples from mice fed methyl-deficient diets. A marked increase in the levels of c-myc and a slight increase in the levels of ornithine decarboxylase and c-H-ras transcripts were seen in the liver RNA samples from the treated mice. Of particular interest was a decrease in the abundance of epidermal growth factor receptor transcripts in the liver RNA samples from the treated mice. These changes in cellular levels of specific RNA resemble, in several respects, those we have previously described in rodent liver during regeneration and tumor promotion and also those seen in rodent hepatomas. They may reflect, therefore, a common profile of gene expression relevant to cell proliferation.
Hsieh
L L
LL
Comprehensive Cancer Center, Columbia University, New York, New York.
Wainfan
E
E
Hoshina
S
S
Dizik
M
M
Weinstein
I B
IB
D000818:Animals; D002455:Cell Division; D002796:Choline Deficiency / Q000235:genetics / Q000503:physiopathology*; D004261:DNA Replication; D005494:Folic Acid Deficiency / Q000235:genetics / Q000503:physiopathology*; D011905:Genes, ras; D007700:Kinetics; D008099:Liver / Q000473:pathology; D008297:Male; D008715:Methionine / Q000172:deficiency*; D008745:Methylation; D051379:Mice; D008815:Mice, Inbred Strains; D009955:Ornithine Decarboxylase / Q000235:genetics; D011519:Proto-Oncogenes; D012016:Reference Values; D012190:Retroviridae / Q000235:genetics / Q000302:isolation & purification*; D014158:Transcription, Genetic; D014806:Vitamin B 12 Deficiency / Q000235:genetics / Q000503:physiopathology*
D008715:Methionine; D009955:Ornithine Decarboxylase