COMPARISON OF 6-THIOGUANINE-RESISTANT MUTATION AND SISTER CHROMATID EXCHANGES IN CHINESE-HAMSTER V79 CELLS WITH 40 CHEMICAL AND PHYSICAL AGENTS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (8) , 3270-3279
Abstract
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 [lung] 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 h 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 vs. SCE-inducing potencies among agents was observed, the maximal difference in the ratios being .apprx. 200-fold. The agents that showed the higher values of the ratio (agents producing more mutations than SCE) were bleomycin, Co-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.cntdot.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 Pt compounds (cis-diamminedichloroplatinum 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.

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