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When papillomas were induced in mouse skin by a single application of 7,12-dimethylbenz[a]anthracene, followed by repeated applications of croton oil, more papillomas appeared when the carcinogen was applied at 10 PM than when given at 10 AM. The average mitotic frequency in the epidermis was lower in the hours following 10 PM than in the hours following 10 AM. It is therefore considered improbable that the carcinogen acts on cells in mitosis. The frequency of epidermal cells synthesizing deoxyribonucleic acid (DNA) preparatory to mitosis was, in contrast, higher in the hours following 10 PM than in those following 10 AM. It is suggested that the carcinogen may act on cells synthesizing DNA.
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Frei et al. (1964) studied this question.
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