Abstract
DNA has been isolated from human bronchial segments that have been treated in short-term organ culture with 3H-labelled benzo (a) pyrene. DNA has also been isolated from mouse skin treated with 3H-labelled samples of benzo (a) pyrene, with the related radioactive 4,5-, 7,8- and 9,10-dihydrodiols and with 3H-3-hydroxybenzo (a) pyrene. Sephadex LH20 column chromatography of hydrolysates of these DNA samples showed that the hydrocarbondeoxyribonucleoside products formed in benzo (a)-pyrene-treated human bronchial mucosa and mouse skin are indistinguishable from those that are formed when 7,8-dihydro-7,8-dihydroxybenzo (a) pyrene 9,10-oxide reacts with DNA in solution. These same hydrocarbon-deoxyribonucleoside products were also found in hydrolysates of DNA from mouse skin treated with 7,8-dihydro-7,8-dihydroxybenzo (a)-pyrene but products of this type were not detected in hydrolysates of DNA following treatment of mouse skin either with the 4,5- or 9,10-dihydrodiols or with 3-hydroxybenzo (a) pyrene. This results show that the metabolic activation of benzo (a) pyrene to a diolepoxide, 7,8-dihydro-7,8-dihydroxybenzo (a) pyrene 9,10-oxide, which reacts with DNA, is the same in human bronchial mucosa, a tissue in which this hydrocarbon is suspected of being carcinogenic, as it is in mouse skin and in hamster embryo cells, two situations in which benzo(a)pyrene is known to induce malignancy.
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