Metabolism of carcinogenic 2-hydroxybenz.
The rates of metabolism of the carcinogenic 2-hydroxybenzo[a]pyrene (2-OH-B[a]P) and the non-carcinogenic 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 non-carcinogenic 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.
Moore
C J
CJ
University of Tennessee-Oak Ridge Graduate School of Biomedical Sciences, Oak Ridge National Laboratory, 37830, USA.
McClusky
G A
GA
Fischer
S M
SM
MacLeod
M C
MC
Slaga
T J
TJ
Selkirk
J K
JK
D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D000078404:Epidermal Cells; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008647:Mesocricetus; D051379:Mice; D018632:Mice, Inbred SENCAR; D012995:Solubility
D001580:Benzopyrenes; D002273:Carcinogens; C021337:9-hydroxybenzo(a)pyrene; C023394:2-hydroxybenzo(a)pyrene; C021338:3-hydroxybenzo(a)pyrene