[Rat microsomal glutathione S-transferase 1 alters cytotoxic effects of chlorambucil on PC-3, K562, HepG2 and P388D1 cell lines].

OBJECTIVE:To explore the possible association between activation of rat microsomal glutathione S-transferase 1 (mGST1) and chlorambucil toxicity on selected cancer cell lines. METHODS:Hepatic microsomes were prepared from male Sprague-Dawley rats and washed to remove cytosolic contamination. mGST1 was purified and its activity was measured. PC-3, K562, HepG2 and P388D1 cell lines were exposed to chlorambucil (CHB) alone or to CHB with mGST1 at concentrations of 0 ~ 100 micromol/L for 8, 24, 48, 72 h. Cytotoxic effects of CHB were determined by cell growth inhibition (MTT assay), mitochondrial transmembrane potential (DeltaPsim), and fluorescence morphological examination (AO/EB staining). RESULTS:The decreased cytotoxic effects of CHB on the cell lines altered by mGST1 were demonstrated in concentration- and time-dependant manners. The CHB-induced apoptosis on PC-3 and K562 cell lines altered by mGST1 was confirmed using DeltaPsim examination, JC-1 or AO/EB staining. CONCLUSION:mGST1 can reduce the cytotoxic effects of CHB in selected cancer cell lines.

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