Protective effect of cysteine against X-ray- and bleomycin-induced chromosomal aberrations and cell cycle delay

Abstract

The protective effect of cysteine was studied in muntjac and human lymphocytes in vitro scoring chromosomal aberrations in harlequin stained first cycle metaphases, induced by X-irradiation at G 0. Its protective efficiency was also studied against the radiomimetic clastogen, bleomycin, in muntjac cells. 30 μg and 1 mg/ml of cysteine were given prior to 2, 3, and 4 Gy, and 2 mg/ml prior to only 4 Gy. 30 μg cysteine protected only against deletions in 4 Gy-treated cells while 1 mg protected against deletions by all three doses of X-rays. However, rearrangements were not reduced significantly in any of these, probably due to their low frequency. But when cysteine was increased to 2 mg, both types of aberrations were reduced significantly. This shows that a sufficient number of aberrations and an optimum concentration of the protector are essential for eliciting the best protective effect. This conclusion is further supported by the results of 2 mg cysteine treatment in human lymphocytes which yielded higher frequencies of rearrangements with 2 and 3 Gy X-rays than 4 Gy in muntjac, but had a relatively lower frequency of deletions. Thus the most abundant categories of aberration, i.e., deletions in muntjac and exchanges in humans, were reduced significantly by 2 mg cysteine, associated with a prominent reduction in the frequency of aberrant metaphases. Therefore, the differential protection observed with a low concentration of the protector and an insufficient yield of aberrations induced only indicates protection provided to the most frequent type of aberration by a protector when present in lower concentration. Cysteine pretreatment yielded weak protection against the effects of bleomycin, but posttreatment caused a mild potentiation of the clastogenic effect of BLM without altering the cell cycle kinetics. In this context, an action of cysteine as a reducing agent on BLM is suggested. Although cysteine alone caused severe retardation of the cell cycle, when given prior to X-irradiation, not only its delaying effect was not observed, but also it reduced the X-ray induced cell cycle delay. This might be due to the oxidation of cysteine by its radical scavenging action.