Comparison of 6-thioguanine-resistant mutation and sister chromatid exchanges in Chinese hamster V79 cells with forty chemical and physical agents.
The induction of sister chromatid exchanges (SCE) and mutation at the hypoxanthine-guanine phosphoribosyl transferase locus and toxicities of 40 different chemical and physical agents were examined on Chinese hamster V79 cells. These agents included mono-, di-, tri-, and polyfunctional alkylating agents, intercalators, gamma-rays, and UV light irradiation. Mutation was measured as resistance to 6-thioguanine and toxicity as loss of cell-plating efficiency. SCE were examined 29 hr after treatment. With the agents examined, a highly positive correlation (r = 0.89) existed between SCE-inducing and mutagenic potencies, when expressed as increase in the number per a unit dose over the control values. But the great difference of the ratios of mutagenic potencies versus SCE-inducing potencies among agents was observed, the maximal difference in the ratios being about 200-fold. The agents that showed the higher values of the ratio (agents producing more mutations than SCE) were bleomycin, cobalt-60 gamma-rays, all ethylating agents (N-ethyl-N-nitrosourea, N-ethyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, and diethylsulfate), N-propyl-N-nitrosourea, N-butyl-N-nitrosourea, isopropyl methanesulfonate, intercalating acridine compounds (2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl)aminopropylamino]-acridine X 2HCl and 2-methoxy-6-chloro-9-[3-(chloroethyl)-aminopropylamino]acridine 2HCl) and UV light at 254 nm. The agents that showed the lower values (agents producing more SCE than mutations) were platinum compounds (cis-diamminedichloro-platinum and trans-diamminedichloroplatinum), epoxides (epichlorohydrin, styrene oxide, and diepoxybutane) and aziridines (mitomycin C, decarbamoyl mitomycin C, tris(1-aziridinyl)phosphine sulfide, triethylenemelamine, and carboquone). The agents that showed the intermediate values included all methylating agents (N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine, methyl methanesulfonate, and dimethyl sulfate), N-(2-hydroxyethyl)ethyleneimine, beta-propiolactone, treatment of 8-methoxypsoralen plus near-UV light irradiation at 352 nm, 4-nitroquinoline-1-oxide, quinacrine mustard, sodium sorbate, cigarette tar, and diesel tar. For most agents that induced SCE, the toxicity dependency of induced SCE was rather biphasic; increase in SCE was steep at low to moderate toxicity and less at moderate to high toxicity. At equitoxic doses, the agents showed great difference in induction of SCE.
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003434:Crossing Over, Genetic / Q000187:drug effects*; D007700:Kinetics; D008168:Lung; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D012854:Sister Chromatid Exchange / Q000187:drug effects* / Q000528:radiation effects; D013329:Structure-Activity Relationship; D013866:Thioguanine / Q000633:toxicity*; D014466:Ultraviolet Rays
D009153:Mutagens; D013866:Thioguanine