Effects of PCB exposure on the toxic impact of organophosphorus insecticides.
Exposure to polychlorinated biphenyls (PCBs) can alter the metabolism of organophosphorus (OP) insecticides. Female rats were fed vanilla wafers containing either 4 mg/kg/day of Aroclor 1254 (PCB-treated) or safflower oil (oil-treated) for 50 days. Rats were then injected, ip, with corn oil, parathion (P=S), methyl parathion (MP=S), chlorpyrifos (C=S), paraoxon (P=O), methyl paraoxon (MP=O), or chlorpyrifos-oxon (C=O). In the livers of rats treated with PCBs but not OP compounds, there was induction of desulfuration (activation) of P=S, MP=S, and C=S, but dearylation (detoxication) was induced only with P=S and MP=S. Hepatic A-esterase hydrolysis of all three oxons was induced. Cholinesterase (ChE) activity was determined in the medulla-pons, hippocampus, corpus striatum, cerebral cortex, skeletal muscle, lung, and heart at 2 and 24 h post exposure. With C=S, P=S, and MP=S, differences in brain ChE inhibition were observed at 2 h (MP=S > P=S > C=S) but few differences were observed between oil- and PCB-treated rats. By 24 h, the level of brain ChE inhibition had increased with P=S and C=S but had decreased with MP=S. In rats exposed to P=S and C=S but not MP=S, ChE inhibition was lower in PCB-treated rats than in oil-treated rats. This suggests that pre-exposure to PCBs has a protective effect against the acute toxicity of P=S and C=S, but not MP=S. This protective effect does not appear to be related to the alteration of the metabolism of these compounds. The slower rate of ChE inhibition following P=S and C=S compared to MP=S suggests that the protection may be mediated by the PCB-induced increase in A-esterase activity. This protection appears to be related to the time between exposure and inhibition of ChE. With the oxons at 2 h, inhibition of ChE was substantial and no differences were present between the PCB- and oil-treated rats. Thus, the rapid rate of inhibition of ChE by the oxons does not afford time for the increase in A-esterase hydrolysis to effectively provide protection against inhibition of ChE. However, while no differences between oil- and PCB-treated rats were observed with MP=O by 24 h, PCB-treated rats exposed to P=O and C=O had lower ChE inhibition than did oil-treated rats with greater differences observed with P=O than C=O.
Carr
Russell L
RL
Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762-6100, USA. rlcarr@cvm.msstate.edu
Richardson
Jason R
JR
Guarisco
John A
JA
Kachroo
Anil
A
Chambers
Janice E
JE
Couch
Terrilyn A
TA
Durunna
Godwin C
GC
Meek
Edward C
EC
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis; D004347:Drug Interactions; D004790:Enzyme Induction; D004950:Esterases / Q000096:biosynthesis; D005260:Female; D006321:Heart / Q000187:drug effects; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D009943:Organophosphorus Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D009943:Organophosphorus Compounds; D020111:Chlorodiphenyl (54% Chlorine); D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D004950:Esterases; D002802:Cholinesterases