In vitro and in vivo induction of heat shock (stress) protein (Hsp) gene expression by selected pesticides.
The chloroacetamide insecticide alachlor, polyhalogenated cyclic hydrocarbons endrin and chlordane and the organophosphate pesticides chlorpyrifos and fenthion induce oxidative tissue damaging effects including lipid peroxidation and nuclear DNA-single strand breaks. The mechanism involved in the induction of oxidative stress by these xenobiotics is unknown. No information is available regarding whether these pesticides can induce the expression of heat shock (stress) protein (Hsp) genes as a common protective mechanism against tissue damage. The pesticides were administered p.o. individually to female Sprague-Dawley rats in two 0.25 LD50 doses at 0 h and 21 h. The animals were killed at 24 h, and liver, brain, heart and lung tissues were removed to examine the induction of Hsps by Western and Northern blot analysis. In a separate series of experiments, cultured neuroactive PC-12 cells were treated 24 h with 50, 100 or 200 nM concentrations of these pesticides. Alachlor, endrin, chlorpyrifos and fenthion induced Hsp89 alpha and Hsp89 beta in hepatic and brain tissues, as well as in cultured PC-12 cells. Chlordane induced some expression of Hsp89 alpha but not Hsp89 beta in the hepatic and brain tissues of treated rats. Some expression of Hsp89 beta was observed in lung tissues of endrin and alachlor treated animals. These findings were substantiated by Western blot analysis using Hsp90 antibody. Except chlordane all these pesticides induced enhanced synthesis of Hsp90 in cultured PC-12 cells. The results indicate striking tissue differences in the patterns of the Hsps induced by the pesticides which were used, and demonstrate that these pesticides can induce the expression of Hsp89 alpha and Hsp89 beta genes in various target organs of rats. The results support the hypothesis that these genes may be mechanistically involved in protecting tissues against oxidative stress induced by structurally diverse pesticides.
Bagchi
D
D
School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178, USA.
Bhattacharya
G
G
Stohs
S J
SJ
D000081:Acetamides / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004390:Chlorpyrifos / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004732:Endrin / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D005260:Female; D005284:Fenthion / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006321:Heart / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects; D010575:Pesticides / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000081:Acetamides; D006360:Heat-Shock Proteins; D010575:Pesticides; C000188:alachlor; D005284:Fenthion; D004390:Chlorpyrifos; D004732:Endrin