Mechanisms of the enhanced liver carcinogenesis by choline in female rats: delay in liver growth after partial hepatectomy and stimulation of 2-AAF mitoinhibition.
Choline given to female rats resulted in an enhanced growth of focal lesions induced by the Solt-Farber model [diethylnitrosamine (DEN) as initiator and 2-acetylaminofluorene (2-AAF) associated with partial hepatectomy (PH) as promoter] when it was administered during promotion, but not during DEN treatment. Based on these data, the mechanisms by which choline might interfere with 2-AAF-PH promotion have been investigated. Compensatory liver growth after PH was faster in females than in males as shown by the restoration of both liver weight and protein content in rats fed a basal diet or a 2-AAF diet. The [3H]thymidine incorporation into DNA occurred a few hours earlier in females than in males. Choline administered to normal females delayed the peak of liver regeneration, by inhibiting [3H]thymidine incorporation into DNA and the mitotic index, resulting in later restoration of liver mass. 2-AAF feeding for 1 week markedly depressed the incorporation of precursor into DNA following PH in both sexes but at greater extent in males. Choline enhanced the mitoinhibition of 2-AAF only in females. No effect of choline was observed in male rats either with or without 2-AAF. The differential effect of choline between sexes in the development of focal lesions appeared to be related to the sexual dimorphism in the 2-AAF mitoinhibition and in the liver proliferation after PH.
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Dipartimento di Medicina ed Oncologia Sperimentale, Corso Raffaello 30, Torino, Italy.
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Dianzani
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D015073:2-Acetylaminofluorene / Q000633:toxicity*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002794:Choline / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004052:Diethylnitrosamine; D004347:Drug Interactions; D005260:Female; D006498:Hepatectomy; D008099:Liver / Q000473:pathology / Q000601:surgery; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008938:Mitosis / Q000187:drug effects*; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013268:Stimulation, Chemical
D004273:DNA, Neoplasm; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D002794:Choline