The effects of several croton oil constituents on DNA repair and cyclic nucleotide levels in cultured mammalian cells

The purpose of this study was to determine the effects of tumor promoters on DNA repair and cyclic nucleotide levels in cultured mammalian cells. Human amnion cells were treated with low doses of either UV or N acetoxy acetylaminofluorene. DNA repair synthesis, measured as 'unscheduled' DNA synthesis, was followed in the absence or presence of 12 O tetradecanoyl phorbol 13 acetate (TPA), phorbol 12,13 dibenzoate (PDB) both potent promoters, or phorbol, a non promoter. These compounds did not inhibit DNA repair synthesis occurring in response to low doses of the carcinogenic agents. In addition, TPA did not inhibit 'post replication' repair occurring in response to UV irradiation of growing Chinese hamster cells. Both TPA and PDB caused rapid increases in cyclic guanosine monophosphate levels in the human cells; phorbol had no effect. None of the croton oil constituents affected cyclic adenosine monophosphate levels. The results will be discussed in light of a possible mechanism of action of tumor promoters involving 'post replication' repair.