The replication of mouse skin epidermal DNA to which is bound 7,12-dimethylbenz(a)anthracene

Experiments were carried out to determine in the intact mouse whether or not mouse skin epidermal DNA to which the polycyclic hydrocarbon DMBA was bound could serve as a template for further DNA replication. Mice which were treated topically with ³H]7,12-dimethylbenz(a)anthracene (³H]DMBA) received 5-bromodeoxyuridine (BUdR) and 5-fluorouracil (5-FU) in order to incorporate BUdR into replicating DNA which was stimulated to undergo synthesis one or two days later. Epidermal DNA was put on a neutral CsCl gradient and binding of ³H]DMBA was found to both replicated and non-replicated DNA. Separation of the BUdR substituted and non-substituted parental strands of newly replicated DNA an on alkaline CsCl, Cs₂SO₄ gradient showed that the great majority of DMBA was bound to parental strand DNA. The possibility that ³H]DMBA binding was taking place at the same time that labeling with BUdR occurred was eliminated. Thus, these experiments showed that in the intact mouse, skin epidermal DNA to which DMBA is bound can serve as a template for further DNA synthesis.