Similarities in lindane induced alteration in cytochrome P450s and associated signaling events in peripheral blood lymphocytes and brain.
Studies were initiated to investigate the similarities in alterations in cytochrome P450s (CYPs) and associated signaling events in brain and peripheral blood lymphocytes (PBL) induced by lindane, an organochlorine pesticide. Adult male albino wistar rats were treated orally with different doses (2.5- or 5.0- or 10- or 15 mg/kg/body weight) of lindane daily for 4 days. In another experiment, the treatment of low dose (2.5mg/kg) of lindane was continued for 15- and 21 days. A dose- and time-dependent increase was observed in the activity of CYP dependent enzymes in brain microsomes and PBL isolated from the treated rats. However, the magnitude of induction was several folds less in PBL. As observed in brain, RT-PCR and Western immunoblotting demonstrated that increase in CYP enzymes in PBL is due to the increase in the mRNA expression of specific CYP isoenzymes. Similarities were also observed in activation of ERK and JNK MAP kinases and c-jun in PBL or brain isolated from rats treated with lindane. Similarities in the induction of CYPs and activation of MAP kinases in PBL and brain suggest that CYP expression profiles in PBL could be used for monitoring the exposure and toxicity of environmental chemicals.
Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226 001, UP, India.
Anwar Jamal
AJ
Khan
Amit
A
Sharma
K
K
Dinesh
Devendra
D
Parmar
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D001556:Hexachlorocyclohexane / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D007306:Insecticides; D012333:RNA, Messenger; D001556:Hexachlorocyclohexane; D003577:Cytochrome P-450 Enzyme System; D020928:Mitogen-Activated Protein Kinases
CYPs; Lindane; Lymphocytes; MAP kinases; Toxicity