Metabolism of carcinogenic 2-hydroxybenzo[a]pyrene in rodent and human cells

Cynthia J. Moore, Gary A. Mcclusky, Susan M. Fischer, Michael C. Macleod, Thomas J. Slaga, James K. Selkirk

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The rates of metabolism of the carcinogenic 2-hydroxybenzo[a]pyrene (2-OH-B[a]P) and the noncarcinogenic 3- and 9-hydroxybenzo[a]pyrenes in cultured cell systems have been studied and compared. While 70-80% of the non-carcinogens are converted to water-soluble derivatives by hamster embryo fibroblasts in 24 h, carcinogenic 2-OH-B[a]P is metabolized at a slower rate (45% in 24 h), comparable to that for the parent hydrocarbon, benzo[a]pyrene (B[a]P). Analysis of extracellular organic solvent-soluble metabolites of 2-OH-B[a]P in cultured hamster embryo fibroblasts, using h.p.l.c., indicates the presence of a single major metabolite, which has been identified by mass spectroscopy as a dihydroxy derivative of B[a]P. At least one additional major organic solvent-soluble metabolite is formed in cultures of either mouse epidermal epithelial cells or human foreskin fibroblasts, indicating a different balance of metabolic pathways in these cell systems. The greater persistence of carcinogenic 2-OH-B[a]P in cells and its higher concentration in the cell cytoplasm compared with the noncarcinogenic phenols may be related to its relatively high biological activity. Differences in metabolism of 2-OH-B[a]P in several cultured cell systems indicate the importance of an appropriate choice of activating system in understanding the relationship between metabolism and carcinogenesis.

Original languageEnglish (US)
Pages (from-to)979-987
Number of pages9
JournalCarcinogenesis
Volume1
Issue number12
DOIs
StatePublished - Dec 1 1980
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research

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