Mitotic aneuploidy as a possible mechanism for tumour promoting activity in bile acids.
A range of conjugated and free bile acids were assayed for their ability to induce a variety of genetic endpoints in growing cells of yeast. None of the bile acids showed any activity in assays for the induction of mitotic crossing-over and mutation whereas the free bile acids lithocholic, chenodeoxycholic, deoxycholic and cholic acid were potent inducers of mitotic chromosome aneuploidy. In contrast, both conjugated bile acids, taurodeoxycholic and glycodeoxycholic lacked the ability to induce mitotic aneuploidy. When the potency of the free bile acids were compared, lithocholic and chenodeoxycholic acids showed higher levels of induction of mitotic aneuploidy per lethal event compared with cholic and deoxycholic acids. In view of the previously observed correlation between the ability of a chemical to induce chromosome aneuploidy and tumour promotional activity, the results indicate that the levels of free bile acids in the colon may be significant factors in the etiology of colonic cancer.
D000782:Aneuploidy; D001647:Bile Acids and Salts / Q000633:toxicity*; D002273:Carcinogens; D002875:Chromosomes / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D007700:Kinetics; D008938:Mitosis / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics; D013329:Structure-Activity Relationship
D001647:Bile Acids and Salts; D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System