Reduced Binding of Carcinogenic Hydrocarbons to DNA of Mouse Skin during Inhibition of DNA Synthesis

Abstract

CARCINOGENIC polycyclic hydrocarbons have been shown to bind to DNA in mouse skin^1–3, but no details are known of the conditions in which this binding occurs in vivo, for example the phase of the cell cycle, the functional status of DNA or whether the DNA is replicating or resting. Data are only available for in vitro binding to denatured and native DNA^3,4. It could be assumed that replicating, histone-free DNA is a better target for hydrocarbons than resting DNA, in which case binding should be reduced if DNA synthesis is blocked. To test this idea we used hydroxyurea in different organisms^5,6; this is a potent and rather specific inhibitor of DNA synthesis, and inhibits more than 90 per cent of DNA synthesis in mouse skin.