The effect of 2-[(aminopropyl)amino] ethanethiol on fission-neutron-induced DNA damage and repair

Abstract

Summary The effect(s) of the radioprotector 2-[(aminopropyl)amino] ethanethiol (WR1065) on fissionneutron-induced DNA damage and repair in V79 Chinese hamster cells was determined by using a neutral filter elution procedure (pH7.2). When required, WR1065, at a final working concentration of 4mM, was added to the culture medium, either 30min before and during irradiation with fission spectrum neutrons (beam energy of 0.85MeV) from the JANUS research reactor, or for selected intervals of time following exposure. The frequency of neutron-induced DNA strand breaks as measured by neutral elution as a function of dose equalled that observed for 60Coy-ray-induced damage (relative biological effectiveness of one). In contrast to the protective effect exhibited by WR1065 in reducing 60Co-induced DNA damage, WR1065 was ineffective in reducing or protecting against induction of DNA strand breaks by JANUS neutrons. The kinetics of DNA double-strand rejoining were measured following neutron irradiation. In the absence of WR1065, considerable DNA degradation by cellular enzymes was observed. This process was inhibited when WR1065 was present. These results indicate that, under the conditions used, the quality (i.e. nature), rather than quantity, of DNA lesions (measured by neutral elution) formed by neutrons was significantly different from that formed by y-rays.WR 1065 is the corresponding free thiol of the wellcharacterised radioprotector S-2-(3-aminopropylamino) ethyl phosphorothioic acid designated WR2721 (Purdie, 1979). The current clinical interest in these and similar compounds stems from early reports that these agents can preferentially protect normal as compared to neoplastic tissues against both acute and late-arising radiation-and/or chemotherapyinduced injuries (Yuhas, 1979;Phillips, 1980;Glover et al., 1984;Kligerman et al., 1984). Thiol compounds such as WR2721 and cysteamine have also been reported to be effective in protecting against oncogenesis in a number of experimental rodent systems (Marquardt et al., 1974;Apffel et al., 1975;Takeuchi & Murakami, 1978;Milas et al., 1984;Grdina et al., 1985b).WR1065 and cysteamine can both protect against radiation induced mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in mammalian cells (Grdina et al., 1985a;Corn et al., 1987). WR1065 has also been found to be effective in protecting against the induction of HGPRT mutants by cisplatin , bleomycin and nitrogen mustard (Nagy & Grdina, 1986) and the transformation of 10T1/2 cells by ionizing radiation (Hill et al., 1986).Linked to the expression of each of these deleterious endpoints are, presumably, factors involving DNA damage and repair. It is well known that selected aminothiol compounds can protect against the induction of single-and double-strand breaks in the DNA of irradiated cells (LaSalle & Billen, 1964;Sawada & Okada, 1970;Billen, 1983;Grdina & Nagy, 1986;Sigdestad et al., 1987;Murray et al., 1988 Accordingly, the US Government retains a non-exclusive, royaltyfree licence to pu...

Amifostine Protective Effect on Cisplatin‐Treated Rat Testis

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Amifostine stimulates formation of multipotent and erythroid bone marrow progenitors

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