Our earlier experiments have shown that the plant phenols-hydroxychavicol, eugenol, catechin, curcumin, and the vitamins--6-carotene and a-tocopherol-are potent inhibitors of polycyclic aromatic hydrocarbon (PAH) induced mutagenesis and carcinogenesis. In an attempt to elucidate their mode of action, we studied their effect on mouse skin DNA synthesis following 7,12 dimethylbenzanthracene (DMBA) treatment and 'H-7,12 dimethylbenzanthracene-DNA interaction in u h o (in the presence of mouse skin S9). With the exception of eugenol, all the phenols and vitamins tested inhibited 'H-DMBA-DNA interaction in uilro. In the DNA biosynthesis assay, of the chemopreventive agents tested only b-carotene effectively modulated DMBA suppressed DNA synthesis in the mouse skin. Our results indicate that the assay of DNA biosynthesis is not of predictive value with respect to the chemopreventive effect of a chemical, while assay of carcinogen-DNA interaction shows correlation between the chemopreventive property and the inhibition of the interaction of carcinogen with DNA.