The metabolism and activation of polycyclic aromatic hydrocarbons in epithelial cell aggregates and fibroblasts prepared from rat mammary tissue |
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Authors: | Cooper, C.S. Pal, K. Hewer, A. Grover, P.L. Sims, P. |
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Affiliation: | Chester Beatty Research Institute, Institute of Cancer Research: Royal Cancer Hospital Fulham Road, London SW3 6JB, UK. |
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Abstract: | The metabolism of 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene(BP) and benz[a]anthracene (BA) by epithelial cell aggregatesand fibroblasts in culture has been investigated using mammarytissue obtained from female Wistar rats. The results show that:(a) both types of mammary cells metabolise all three hydrocarbonsinto ether- and water-soluble derivatives; (b) the patternsof metabolites produced by epithelial cells and fibroblastsare similar but that fibroblasts form more of the water-solublematerials; (c) the major dihydrodiols formed are the 8,9-dihydrodiolsof BA and DMBA and the 7,8- and 9,10-dihydrodiols of BP; (d)all three hydrocarbons are metabolised to form products thatbind covalently to protein but only the potent carcinogens BPand DMBA are metabolised to form derivatives that react covalentlywith DNA; and (e) the chromatographic profiles of the hydrocarbon- deoxyribonudeoside adducts formed in epithelial cells treatedwith either BP or DMBA are similar to those obtained in analogousexperiments with fibroblasts. |
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