Protective effects of 2-[(aminopropyl)amino] ethanethiol against bleomycin and nitrogen mustard-induced mutagenicity in V79 cells

Abstract

This study examines the effects of the radioprotector 2-[(aminopropyl)amino] ethanethiol (WR1065) on bleomycin (BLM) and nitrogen mustard- (HNZ) induced cytotoxicity, DNA damage, and mutagenesis at the hypoxanthineguanine phosphoribosyl transferase (HGPRT) locus in V79 Chinese hamster cells. The anti-mutagenic effect of WR1065 on cis-diamminedichloroplatinum (cis-DDP) and radiation- (XRT) induced HGPRT mutations was also evaluated for comparative purposes. WR1065 (4 mM) was added prior to exposure of cells to therapy agents. All exposure times were 30 min. and both cell survival and mutagenesis were assayed. WR1065 was effective in protecting against both effects. The induction of mutants corrected for background by BLM, HN 2, cis-DDP, or XRT was linear in all cases. Mutation frequencies without WR1065 were 78 X 10 −6 per unit BLM, 66 X 10 −7 per μg HN 2, 25 X 10 −7 per μg cis-DDP; and 87 X 10 −7 per Gy of XRT. With WR1065, these were reduced to 37 × 10 −6 per unit BLM, 40 X 10 −7 per μg cis-DDP, and 44 × 10 −7 per Gy of XRT. Mutation protection factors (MPF), a ratio of the corresponding slopes of the mutation induction curves, with and without WR1065 were: BLM, MPF = 2.8; HN 2, MPF = 3.4; cis-DDP, MPF = 7.1; and XRT, MPF = 5.1. Single-strandbreak (SSB) formation in DNA by BLM or HN 2, assayed by alkaline elution, was protected against by WR1065. WR1065 did not induce SSB in control cells. The reduction of the mutagenic effects of agents used in radiation and chemotherapy by radioprotectors may be an important additional benefit for consideration in their use in cancer treatment.