Comparative studies on lipid peroxidation and DNA-single strand breaks induced by lindane, DDT, chlordane and endrin in rats.
1. A variety of structurally dissimilar polyhalogenated cyclic hydrocarbons produce similar toxic effects. The molecular mechanisms involved in the production of these toxic manifestations is not known. 2. We have proposed that reactive oxygen species may be involved, and have therefore examined the time-dependent effects of lindane (30 mg/kg), DDT (40 mg/kg), chlordane (120 mg/kg), and endrin (4.5 mg/kg) on the production of hepatic mitochondrial and microsomal lipid peroxidation and DNA single strand breaks, two indices of oxidative stress. 3. All four xenobiotics resulted in significant increases in hepatic lipid peroxidation and DNA damage. Earliest (6 hr) increases in both lipid peroxidation and DNA damage were observed following lindane administration. Time-dependent increases in both parameters were observed following endrin administration. 4. Maximum increases in DNA single strand breaks of 2.8- and 2.5-fold were observed 12 hr after DDT and chlordane administration, respectively, while a 4.4-fold increase was observed 24 hr after endrin administration. 5. The results demonstrate that the four structurally dissimilar polyhalogenated hydrocarbons produce oxidative tissue damage which may contribute to the toxic manifestations of these xenobiotics, and exhibit different toxicokinetic properties.
Hassoun
E
E
School of Pharmacy and Allied Health Professions, Creighton University Health Sciences Center, Omaha, NE 68178.
Bagchi
M
M
Bagchi
D
D
Stohs
S J
SJ
D000818:Animals; D002706:Chlordan / Q000633:toxicity; D003634:DDT / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000187:drug effects*; D004732:Endrin / Q000633:toxicity; D005260:Female; D001556:Hexachlorocyclohexane / Q000633:toxicity; D007306:Insecticides / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004277:DNA, Single-Stranded; D007306:Insecticides; D002706:Chlordan; D001556:Hexachlorocyclohexane; D003634:DDT; D004732:Endrin