title: 4NQO- or MNNG-resistant variants established from a human cell line, RSb, with high sensitivity to both agents.
abstract: From a human cell line, RSb, with high sensitivity to the killing effects of 4-nitroquinoline 1-oxide (4NQO), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 254-nm ultraviolet light, a 4NQO-resistant variant, Qr-10, and an MNNG-resistant one, Gr-10, were established using ethyl methanesulfonate as the mutagen. Cell proliferation studies and colony-formation assays revealed that Qr-10 and Gr-10 cells actively proliferated under conditions where RSb cell proliferation was greatly inhibited by 4NQO and MNNG, respectively. Total cellular DNA synthesis, as estimated by [Me-3H]thymidine uptake into acid-insoluble cell materials, was depressed in 4NQO-treated Qr-10 and MNNG-treated Gr-10 cells as it was in chemical-treated RSb cells, but recovered more markedly from such inhibition in the variants. 4NQO- and MNNG-induced DNA-repair replication synthesis was enhanced to a greater extent in Qr-10 and Gr-10 cells, respectively, than in RSb cells. The Qr-10 and Gr-10 cells showed the same respective susceptibility to the effects of MNNG and 4NQO, on cell growth and DNA synthesis and DNA-repair synthesis as did the parent cells. But, Qr-10 cells had more resistance to UV-killing and higher levels of UV-induced DNA-repair synthesis than did RSb cells, while UV-susceptibility of Gr-10 cells was the same as that of the latter.
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D004351:Drug Resistance; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D009600:Nitroquinolines / Q000633:toxicity*; D014466:Ultraviolet Rays
chemical_list: D009600:Nitroquinolines; D008769:Methylnitronitrosoguanidine; D015112:4-Nitroquinoline-1-oxide; D004247:DNA