Cytotoxicity and keratinocyte microsome-mediated mutagenic activation of carcinogens in cultured epidermal cells

Hyang Sook Chun, Paul A. Kuzmicky, Laura Rucoba, Norman Y. Kado, Robert H. Rice

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Four model carcinogens (aflatoxin B1, 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 B1, Trp-P-1 and Trp-P-2 were tested for activation by microsomes isolated from these cells in a bacterial mutagenesis assay. Treated rat cultures exhibited sensitivity to Trp-P-1 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 AFB1 were stimulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), consistent with their dependence on the biotransformation reactions this agent induces; however, the toxicity correlated poorly with observed bacterial mutagenicity mediated by their isolated microsomes. 6-Nitrochrysene, a known direct-acting mutagen in bacteria, was highly toxic to the rat but not to the human cells. Since toxic effects can modify carcinogenic outcomes, these findings are compatible with a complex relationship between toxicity, mutagenicity and carcinogenicity and indicate the utility of keratinocytes for clarifying this relationship. (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)165-172
Number of pages8
JournalToxicology Letters
Volume115
Issue number2
DOIs
StatePublished - May 19 2000

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Keywords

  • Aflatoxin
  • Cytochrome P450
  • Nitroaromatics
  • TCDD
  • Trp-P-1
  • Trp-P-2

ASJC Scopus subject areas

  • Toxicology

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