Choline enhances acetylaminofluorene promotion of liver carcinogenesis in female but not in male rats

Abstract

The growth of focal lesions during chemical carcinogenesis has been analyzed after promotion in the liver of female and male rats receiving choline for 4 or 5 weeks. The number and size of foci of altered hepatocytes were first evaluated after methylnitrosourea was used as initiator and 2-acetylaminofluorene (2-AAF) associated with carbon tetrachloride as promoter. The development of enzyme-altered foci was lower in female rats than in males. Choline given intragastrically stimulated the growth of focal lesions in female rats by increasing both the enzyme-positive area of the single focus and the total area of positive foci per cm2 of liver section up to levels close to those of males. No effect of choline was observed in males. In a second set of experiments, focal proliferative lesions induced with the Solt-Farber model were larger in females fed a choline-enriched diet during the promotion phase, as a result of the area of the focus and the total area of foci per cm2 of liver being higher than that in females not receiving choline, with no significant change in the number of foci. When cell proliferation was selected during promotion by 2-AAF and carbon tetrachloride instead of partial hepatectomy, the effect of the choline-enriched diet was even more pronounced. This difference might be accounted for by the greater hepatotoxicity of xenobiotics after choline administration. The hypothesis that choline may enhanced hepatocyte susceptibility towards 2-AAF action by an increase in drug toxicity is discussed.