INFLUENCE OF DURATION OF EXPOSURE TO STYRENE OXIDE ON SISTER-CHROMATID EXCHANGES AND CELL-CYCLE KINETICS IN CULTURED HUMAN BLOOD-LYMPHOCYTES IN-VITRO

Styrene-7,8-oxide, an intermediate of styrene, is a known alkylating m utagen. The present study was carried out to investigate the influence of duration of exposure to styrene-7,8-oxide (styrene oxide) on induc tion of sister chromatid exchanges (SCEs) and inhibition of cell-cycle kinetics using cultured human blood lymphocytes in vitro. Phytohemagg lutinin-stimulated whole-blood lymphocyte cultures obtained from hepar inized whole blood from healthy donors were exposed to 100 mu M styren e oxide for 22, 36, 48 and 72 h. A reduction of SCEs induction with in crease in duration of exposure to styrene oxide was observed, i.e. a c lear significant inverse relationship between exposure time and freque ncies of SCEs induction due to styrene oxide was obtained. Styrene oxi de induces significant elevations in unscheduled DNA synthesis DNA rep air as well as S-phase synthesis in human blood lymphocytes in vitro, depending on the duration of exposure. The decrease in the induction o f SCEs due to styrene oxide with increasing duration of its exposure m ay be principally due to an increased DNA repair and partly due to an increasing metabolic transformation to styrene glycol with increasing duration of its exposure as well as to some extent due to cell death a t the maximum period of exposure, i.e. 72 h. Although the proliferatio ns of lymphocytes exposed to 100 mu M styrene oxide were significantly inhibited at different durations of exposure, no linear relationship between the replication index and the duration of exposure was noticed (r = 0.47, p > 0.05). Similarly, there was no relationship between re plication index and SCE frequency (r = -0.36, p > 0.05), suggesting th at these two parameters may reflect two different endpoints for the cy togenotoxic effects of styrene oxide. (C) 1997 Elsevier Science B.V.