Selective toxicity in putative preneoplastic hepatocytes: a comparison of hydroquinone and duroquinone.
In this paper data is presented suggesting selective toxicity towards enzyme altered hepatocytes. Hydroquinone (HQ) treatment 24 or 48 h after diethylnitrosamine (DEN) initiation reduced the number of glutathione S-transferase-P (GST-P)-positive hepatocytes in situ. Furthermore, in experiments on primary cultures of hepatocytes from control rats a synergism in cell killing between DEN and HQ was observed. In another in vitro system the effect of HQ and duroquinone (DQ) on GGT-positive and -negative hepatocytes was investigated. DQ was shown to affect the GGT-positive cells, while HQ mainly affected GGT-negative cells. These results suggest that HQ can reduce the population of enzyme altered foci (EAF) precursor cells by synergistic interactions with DEN, but provide no support for the notion that HQ selectively damage cells in developed EAF. This conclusion is supported by previously published data on effects of HQ on the development of EAF.
Stenius
U
U
Department of Toxicology, National Institute of Occupational Health, Solna, Sweden.
Warholm
M
M
Högberg
J
J
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D002478:Cells, Cultured; D004052:Diethylnitrosamine / Q000494:pharmacology; D004357:Drug Synergism; D004790:Enzyme Induction; D005260:Female; D006873:Hydroquinones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D011230:Precancerous Conditions; D051381:Rats; D017207:Rats, Sprague-Dawley
D016227:Benzoquinones; D006873:Hydroquinones; D004052:Diethylnitrosamine; C034257:duroquinone; C031927:hydroquinone