[Rat microsomal glutathione S-transferase 1 alters cytotoxic effects of chlorambucil on PC-3, K562, HepG2 and P388D1 cell lines].
To explore the possible association between activation of rat microsomal glutathione S-transferase 1 (mGST1) and chlorambucil toxicity on selected cancer cell lines.



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).



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.



mGST1 can reduce the cytotoxic effects of CHB in selected cancer cell lines.
Chen
Zhe
Z
Institute of Pharmacology & Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Ye
Zi-qi
ZQ
Shi
Qiang
Q
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002699:Chlorambucil / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil; D005982:Glutathione Transferase