Mouse keratinocytes derived from initiated skin or papillomas are resistant to DNA strand breakage by benzoyl peroxide: a possible mechanism for tumor promotion mediated by benzoyl peroxide

Abstract

Alkaline elution was used to examine DNA single-strand breaks in cultured normal and carcinogen-altered mouse keratinocytes exposed to 12-O-tetradecanoyl phorbol-13-acetate and benzoyl peroxide. Seven cell lines derived from carcinogen-induced mouse skin papillomas and three cell lines derived from N-methyl-N'-nitro-N-nitrosoguanidine-treated non-tumor bearing mouse skin were resistant to phorbol ester-mediated DNA strand breaks after 6 or 24 h. Normal keratinocytes sustained strand breaks after 24 h but not after 6 h. Benzoyl peroxide induced extensive strand breaks in normal keratinocytes at both 6 and 24 h, and this was associated with marked cytotoxicity. In contrast, 9 of 10 cell lines showed complete or partial resistance to strand breaks following benzoyl peroxide exposure. It is proposed that differential resistance to DNA strand breaks and cytotoxicity among normal and carcinogen-altered keratinocytes provides the biological basis for the promoting action of benzoyl peroxide. Furthermore, sublethal DNA damage in preneoplastic or neoplastic keratinocytes may account for the potency of benzoyl peroxide in causing malignant conversion.