Ah. Hammond et Jr. Fry, INVOLVEMENT OF CYTOCHROME P4502E1 IN THE TOXICITY OF DICHLOROPROPANOLTO RAT HEPATOCYTE CULTURES, Toxicology, 118(2-3), 1997, pp. 171-179
Hepatocytes were isolated and cultured from untreated rats and rats tr
eated with isoniazid to induce cytochrome P4502E1. Isoniazid selective
ly increased p-nitrophenol hydroxylase activity in 2-h cultures, and i
ncreased the toxicity of both 1,3- and 2,3-dichloropropanol. Isoniazid
also increased the rate and extent of glutathione depletion by the di
chloropropanols. There was no effect of isoniazid on the toxicity of 1
,3-dichloroacetone, precocene II or allyl alcohol. In addition, diethy
ldithiocarbamate selectively inhibited p-nitrophenol hydroxylase in 2-
h cultures from untreated and isoniazid-treated rats, as well as aboli
shing toxicity of the dichloropropanols. In 24-h cultures from isoniaz
id-treated rats diethyldithiocarbamate inhibited high affinity MCOD ac
tivity by 55% and there was also a small but significant inhibition of
precocene II toxicity. These results indicate that isoniazid-inducibl
e P4502E1 can mediate the toxicity of dichloropropanol. (C) 1997 Elsev
ier Science Ireland Ltd.