Induction of aryl hydrocarbon hydroxylase and DNA adduct formation in parental and carcinogen transformed C3H/10T1/2 clone 8 cells by benzo[a]pyrene |
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Authors: | M B Faletto A E Maccubbin P L Koser J A Vangalio H L Gurtoo |
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Institution: | Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, New York 14263. |
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Abstract: | C3H/10T1/2 clone 8 (10T1/2) cells possess aryl hydrocarbon hydroxylase (AHH) activity capable of metabolizing polycyclic aromatic hydrocarbons to ultimate carcinogenic forms. AHH activity in 10T1/2 cells was measured before and after culturing in the presence of benzoa]pyrene (Ba]P), and compared to the AHH activity found in carcinogen-transformed 10T1/2 cell lines treated similarly. The cell lines were also examined for Ba]P-DNA adduct formation, using the 32P-postlabelling technique. Treatment of parental 10T1/2 cells with Ba]P was found to significantly increase AHH activity and produce substantial numbers of DNA adducts. In addition to a major Ba]P-DNA adduct, 5-6 minor DNA adducts were also detected. Relative to parental 10T1/2 cells, an aflatoxin B1-transformed 10T1/2 cell line (7SA) was found to have significantly depressed AHH activity. In addition, after treatment with Ba]P, 7SA cells had only 8% of the Ba]P-DNA adduct levels found in 10T1/2 cells. This system may provide an in vitro model for investigating mechanisms responsible for the depression of cytochrome P-450 activities by chemical carcinogens. |
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