3-AMINO-1,4-DIMETHYL-5H-PYRIDO[4,3-B]INDOLE (TRP-P-1) SENSITIZES MAMMALIAN-CELLS TO UV-RADIATION BY CAUSING THE S-PHASE ARREST, NOT BY INHIBITING THE REPAIR OF DNA-DAMAGE AS OBSERVED IN ESCHERICHIA-COLI

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) is known to be a mutagen and carcinogen isolated from the charred parts of cooked food s. We found previously that Trp-P-1 enhanced UV-induced lethality and mutation frequency in Escherichia coli by inhibiting the repair of UV- induced DNA damage. In the present study. we investigated whether Trp- P-1 also potentiated UV-induced lethality by inhibiting the repair of UV-induced DNA damage in cultured mammalian cells. As a result, Trp-P- 1 enhanced UV-induced lethality in a concentration-dependent manner in human and Chinese hamster cells. However, Trp-P-1 was unable to inhib it the repair of the two major photolesions (cyclobutane pyrimidine di mers and (6-4)photoproducts) from the genomic DNA, as determined using monoclonal antibodies specific for each type of lesion. On the other hand, Trp-P-1, with or without UV irradiation, efficiently suppressed DNA synthesis and arrested cells in S phase in concentration-and time- dependent manners. as measured by pulse-labelling with H-3-thymidine a nd flow cytometry. Thus, the present results suggest that Trp-P-1 pote ntiates UV-induced lethality in cultured mammalian cells by causing th e S-phase arrest, not by inhibiting the repair of UV-induced DNA damag e as observed in Escherichia coli.