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Metabolism of carcinogenic 2-hydroxybenzo(a)pyrene in rodent and human cells

Journal Article · · Carcinogenesis (N.Y.); (United States)

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 to 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.

DOE Contract Number:
W-7405-ENG-26
OSTI ID:
5543549
Journal Information:
Carcinogenesis (N.Y.); (United States), Journal Name: Carcinogenesis (N.Y.); (United States) Vol. 1:12; ISSN CRNGD
Country of Publication:
United States
Language:
English