Antipain-mediated suppression of sister chromatid exchanges induced by an inhibitor of poly (ADP-ribose) polymerase.

Abstract

Exposure of mammalian cells to inhibitors of poly(ADP-ribose) polymerase, such as 3-aminobenzamide (3AB) results in the induction of sister chromatid exchanges (SCEs). The mechanism for the induction of SCEs by 3AB is unknown but is thought to be related to the incorporated halogenated pyrimidine used in SCE analysis. In this characteristic, 3AB-mediated SCE induction is similar to the elevated SCE frequency found in Bloom's syndrome (BS) cells. Recently, it has been reported that certain protease inhibitors, such as antipain, will inhibit SCE induction in BS cells. We now report that antipain will also suppress 3AB-induced SCE frequency. As has been reported for BS cells, the effects of antipain on SCE induction are partial, reducing SCE frequency by 0.15 to 0.40 SCE/chromosome (5-25% of the total induced frequency), and 30 microM concentrations of antipain are saturating. Antipain has no effect on baseline SCE frequency. These effects appear to involve free-radical production because dimethylsulfoxide (DMSO), a free-radical scavenger, will mimic the effects of antipain on 3AB-induced SCEs. Both antipain and DMSO will also reduce the elevated SCE frequency found in cells exposed to high (100 microM or more) levels of bromodeoxyuridine (BrdUrd). High exogenous levels of BrdUrd produce some of the same biological effects as 3AB exposure. Thus, a minor fraction of the elevated SCE frequency seen in cells exposed to 3AB or to high levels of BrdUrd appears to be similar to that found in cultured BS cells and is probably due to some free-radical-producing process.