Abstract:
: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 foods. 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 inhibit the repair of the two major photolesions (cyclobutane pyrimidine dimers 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 3H-thymidine and flow cytometry. Thus, the present results suggest that Trp-P-1 potentiates UV-induced lethality in cultured mammalian cells by causing the S-phase arrest, not by inhibiting the repair of UV-induced DNA damage as observed in Escherichia coli.
journal_name
J Radiat Resjournal_title
Journal of radiation researchauthors
Mori T,Nakagawa A,Kobayashi N,Hashimoto MW,Wakabayashi K,Shimoi K,Kinae Ndoi
10.1269/jrr.39.21subject
Has Abstractpub_date
1998-03-01 00:00:00pages
21-33issue
1eissn
0449-3060issn
1349-9157journal_volume
39pub_type
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