Hs. Chun et al., Cytotoxicity and keratinocyte microsome-mediated mutagenic activation of carcinogens in cultured epidermal cells, TOX LETT, 115(2), 2000, pp. 165-172
Four model carcinogens (aflatoxin B-1, 6-nitrochrysene, 3-amino-1-dimethyl-
5H-pyrido[4.3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (
Trp-P-2)) were examined for their ability to inhibit the growth of cultured
human and rat epidermal cells. To find a basis for observed differences in
growth inhibition, aflatoxin B-1, Trp-P-1 and Trp-P-2 were tested for acti
vation by microsomes isolated from these cells in a bacterial mutagenesis a
ssay. Treated rat cultures exhibited sensitivity to Trp-P-l and Trp-P-2 and
especially aflatoxin toxicity (growth inhibition) despite their microsomes
being unable to induce bacterial mutagenicity. In treated human cultures,
the toxicities of Trp-P-1, Trp-P-2 and AFB(1) were stimulated by 2,3,7,8-te
trachlorodibenzo-p-dioxin (TCDD), consistent with their dependence on the b
iotransformation reactions this agent induces; however, the toxicity correl
ated poorly with observed bacterial mutagenicity mediated by their isolated
microsomes. 6-Nitrochrysene, a known direct-acting mutagen in bacteria, wa
s highly toxic to the rat but not to the human cells. Since toxic effects c
an modify carcinogenic outcomes, these findings are compatible with a compl
ex relationship between toxicity, mutagenicity and carcinogenicity and indi
cate the utility of keratinocytes for clarifying this relationship. (C) 200
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