Enhanced genotoxicity by melphalan and hyperthermia in chronic heroin addicts

Spontaneous melphalan- (MEL-) and MEL-hyperthermia- (MEL-HYP-) induced sister chromatid exchange (SCE) frequencies have been studied in 12 chronic heroin addicts (HER AD) and in 12 age- and sex-matched healthy controls. The incidence of spontaneous SCEs in lymphocytes from the HER AD was significantly greater (P < 0.001) than those from the control subjects. When exposed to MEL in vitro, cells from both groups showed an increase in SCE frequency with yields from HER AD higher than those from controls. When exposed to MEL and hyperthermia (41.5°C for 3 h) in vitro, cells from both groups showed further increases in SCE frequency with yields from HER AD higher than those from controls. We observed that hyperthermia (HYP) in combination with MEL synergistically enhances SCEs and cell division delays in both groups, with the synergistic effects in cells from HER AD higher than those from controls.