Resistance to hepatotoxins acquired by hepatocytes during liver regeneration.
The appearance of resistance to a number of hepatotoxins in primary cultures of hepatocytes prepared at various time intervals up to 2 weeks after partial hepatectomy is the major focus in this study. Resistance to the cytocidal effect of aflatoxin B1, 2-acetylaminofluorene, N-hydroxy-2-acetylaminofluorene, methotrexate, or methyl methanesulfonate shows a progressive increase until 48 hr and then returns to the resting level of susceptibility by 2 weeks. The genesis of mutagens from 2-acetylaminofluorene and aflatoxin B1 by S-9 liver fractions shows a decrease from and return to control values after partial hepatectomy that parallels the resistance. The levels of total cellular cytochromes P-450 also decrease following partial hepatectomy and remain from 28 to 36% less than those of controls for at least 1 week. The glutathione and total soluble sulfhydryl ("glutathione") content increase following partial hepatectomy, and the pattern is consistent with a partial role for glutathione in the resistance phenomenon as it relates to 2-acetylaminofluorene. The possible relationship between resistance to the cytocidal effects in vitro and the resistance to inhibition of cell proliferation in vivo during liver carcinogenesis is discussed.
D015073:2-Acetylaminofluorene / Q000633:toxicity; D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D004351:Drug Resistance; D006881:Hydroxyacetylaminofluorene / Q000633:toxicity; D008099:Liver / Q000187:drug effects*; D008115:Liver Regeneration; D008297:Male; D008727:Methotrexate / Q000633:toxicity; D008741:Methyl Methanesulfonate / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D000348:Aflatoxins; D006881:Hydroxyacetylaminofluorene; D015073:2-Acetylaminofluorene; D016604:Aflatoxin B1; D008741:Methyl Methanesulfonate; D008727:Methotrexate