Influence of Bromobenzene on the Induction of Skin Tumors by 3,4-Benzpyrene

It has previously been demonstrated that the rate of tumor induction in mice by chemical carcinogens of the hydrocarbon type is retarded by a series of compounds containing labile halogen atoms (9, 10). These halogen compounds ranged from chloro-acetal, a compound of relatively low reactivity, to a variety of highly active acid halides. The velocity constants of their reaction with cysteine under physiological conditions and their power of checking cell glycolysis followed the same order and ran parallel with their capacities for retarding tumor induction. The question arose whether the inhibition of the glycolytic process was the effective determinant of the slowing of the carcinogenic process, since, in addition to this action, all the compounds used could affect other cell mechanisms by fixation of sulphydryl groups. This more generalized concept, that disturbances of sulphur metabolism interfere with carcinogenic action, seemed worthy of investigation. For this purpose, substances were required that would affect sulphur metabolism but be devoid of direct, specific action on the glycolytic mechanism. Compounds eliminated as mercapturates should fulfil this role, provided that detoxication occurred locally in the skin. The literature dealing with the elimination of bromobenzene and allied substances describes the liver as the principal site of detoxication, since the toxic substances were normally administered via the stomach. Evidence will be given that bromobenzene can also be detoxicated in the skin and that its application to an area of skin under the influence of a carcinogen effectively retards, and sometimes prevents, the completion of the carcinogenic process. Since the glycolysis-checking compounds with their active halogen atoms, and bromobenzene with a halogen atom unreactive in the same sense, have the common property of disturbing sulphur metabolism, the inference is made that the latter is the biochemical basis of their anticarcinogenic action.