Stereoselective aspects of the metabolic activation of benzo[ a]pyrene by human skin in vitro

Abstract

Benzo[ a]pyrene (BP) is activated within tissues in both a regio- and a stereoselective manner and, since human skin is sensitive to tumour induction by polycyclic aromatic hydrocarbons (PAH), the stereoselective metabolism of BP in this tissue has been investigated. Samples of skin from eleven individuals were treated with [ 3H]BP in short-term organ culture. Two samples were also treated with mixtures of [ 14C](+)- and (−)- trans-7,8-dihydro-7,8-dihydroxybenzo[ a]pyrene (BP-7,8-dihydrodiol) in varying proportions. Following application of [ 3H] BP, more 7,8-dihydrodiol was recovered from the skin itself than from the culture fluid in ten cases; no 7.8-dihydrodiol was detected in extracts from the eleventh. The 7,8-dihydrodiol metabolite was extracted predominantly (range 74–99%) as the (−)-enantiomer in nine of these ten patients, although proportionately more (+)-enantiomer was recovered from the culture fluid than from the skin in each case. The relative proportions of [ 3H]BP tetrols derived from syn- and anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydroxybenzo[ a]pyrene (BPDE) detected in these extracts was more variable. When skin samples were treated with [ 14C]BP-7,8-dihydrodiol, more anti- than syn-BPDE-derived tetrols were extracted, irrespective of the optical purity of the dihydrodiol applied. These findings provide evidence for interindividual variations in the stereoselective metabolism of BP, which may be of some importance in determining individual susceptibility to PAH-induced skin carcinogenesis.