Erythrocyte-Dependent Metabolic Activation of Styrene and Induction of Sister Chromatid Exchange in Cultured Human Lymphocytes

Abstract

Human erythrocytes can oxidize styrene to styrene-7,8-oxide in the absence of the co-factors required for metabolic reactions catalysed by the microsomal cytochrome P-450 system. This probably explains the increased incidence of sister chromatid exchanges (SCEs) that was detected in whole blood lymphocyte cultures from 11 male donors after treatment in vitro (48 h) with styrene (2 mM). Styrene-7,8-oxide (0.15 mM) also induced SCEs in these cultures. Styrene (0.5–4.0 mM) increased the incidence of SCEs only slightly in cultures of isolated lymphocytes (2 × 10⁴ erythrocytes/ml), but had a clear dose-dependent effect in whole blood cultures (2–4 × 10⁸ erythrocytes/ml). When erythrocytes were added to purified cultures, SCE incidence increased after treatment with styrene (2 mM). Cyclophosphamide elevated the incidence of SCEs almost equally efficiently in whole blood and in isolated lymphocytes. It is suggested that styrene induces SCEs after transformation to styrene-7,8-oxide by oxyhemoglobin in erythrocytes, whereas cyclophosphamide is activated by the lymphocytes themselves.