The structure and function of the H-ras proto-oncogene are not altered in rat liver tumors initiated by 2-acetylaminofluorene, 2-acetylaminophenanthrene and trans-4-acetylaminostilbene.
Liver tumors were generated in Wistar rats in an initiation-promotion experiment. 2-Acetylaminofluorene (AAF), 2-acetylaminophenanthrene (AAP), and trans-4-acetylaminostilbene (AAS) were administered to newborn animals as initiators, and phenobarbital as a promoter was added to the drinking water after weaning. Livers were examined after 26, 52, 78, and 104 weeks. Tumors were present in all groups except for at the first time point. The potency of the initiators decreased in the order AAS > AAP > AAF. DNA from tumors of all groups and of control livers was analyzed for mutations in the H-ras gene, but no mutations could be found. The sequence of almost the entire H-ras gene was determined and was compared to other H-ras genes. There are some differences with the sequence in other rat strains, particularly in intron D containing the alternative splicing site. The expression of the H-ras gene has also been studied by various methods in enzyme altered foci and tumors, but no alterations could be found. It is, therefore, concluded that structural of functional alterations of this proto-oncogene are not involved in the generation of liver tumors in Wistar rats by the three genotoxic arylamines.
Bitsch
A
A
Institut für Toxikologie, Universität Würzburg, Germany.
Röschlau
H
H
Deubelbeiss
C
C
Neumann
H G
HG
D015073:2-Acetylaminofluorene / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002273:Carcinogens / Q000494:pharmacology*; D004252:DNA Mutational Analysis; D005260:Female; D011905:Genes, ras / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012689:Sequence Homology, Nucleic Acid; D013267:Stilbenes / Q000494:pharmacology*
D002273:Carcinogens; D010616:Phenanthrenes; D013267:Stilbenes; C028520:4-acetylaminostilbene; C026364:2-acetamidophenanthrene; D015073:2-Acetylaminofluorene