Generation of Reactive Oxygen Species, DNA Damage and Lipid Peroxidation in Liver by Structurally Dissimilar Pesticides

  • S. J. Stohs
  • D. Bagchi
  • M. Bagchi
  • E. A. Hassoun


The structurally dissimilar polyhalogenated cyclic hydrocarbons (PCH), chlorinated acetamide herbicides (CAH) and organophosphate insecticides (OPS) are classified as pesticides or contaminants of pesticides, and/or environmental pollutants. PCH such as endrin and chlordane, and CAH such as alachlor are halogenated and lipophilic [1–3], while OPS as fenthion and chlorpyrifos are organic triesters of phosphoric acid and phosphorothioic acid and are also lipophilic and highly toxic [3].


Lipid Peroxidation Liver Homogenate Single Strand Break Hepatic Lipid Peroxidation Oxidative Tissue Damage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Murphy, R. and Harvey, C. (1985). Residues and metabolites of selected persistent halogenated hydrocarbons in blood specimens from a general population survey, Environ. Hlth. Persp., Vol. 60, pp. 115–120.CrossRefGoogle Scholar
  2. 2.
    Kimbrough, R.D. (1985). Laboratory and human studies on polychlorinated biphenyls (PCBs) and related compounds, Environ. Hlth. Persp., Vol. 59, pp. 99–106.CrossRefGoogle Scholar
  3. 3.
    Murphy, S.D. (1986). Toxic effects of pesticides, In Toxicology: The Basic Science of Poisons, 3rd ed. ( C.D. Klassen, M.V. Amdur and J. Doull, Eds.) pp. 519–581. McMillan Publishing Co., New York.Google Scholar
  4. 4.
    Shain, W., Bush, B. and Seegal, R. (1991). Neurotoxicity of polychlorinated biphenyls: Structure-activity relationship of individual congeners, Toxicol. Appl. Pharmacol., Vol. 111. pp. 33–42.CrossRefGoogle Scholar
  5. 5.
    Bach, D. and Sela, B.A. (1984). Interaction of the chlorinated hydrocarbon insecticide lindane or DDT with lipids-a differential scanning calorimetry study, Biochem. Pharmacol., Vol. 33, pp. 2227–2230.Google Scholar
  6. 6.
    Poland, A. and Knutson, J.D. (1982). 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity, Ann. Rev. Pharmacol. Toxicol., Vol. 22, pp. 517–554.Google Scholar
  7. 7.
    Viviani, A., Lutz, W.K. and Schlatter,.C. (1978). Time course of the induction of aryl hydrocarbon hydroxylase in rat liver nuclei and microsomes by phenobarbital, 3-methyl cholanthrene, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, dieldrin, and other inducers, Biochem. Pharmacol., Vol. 27, pp. 2103–2108.Google Scholar
  8. 8.
    Pinter, A., Torok, G., Surjan, A., Csik, M., Borzsonyi, M. and Kelescsenyi, Z. (1989). Genotoxicity of selected herbicides, Ann. 1st Super Sanita Vol. 25, pp. 577–582.Google Scholar
  9. 9.
    Plewa, M.J., Wagner, F.D., Gentile, G.J. and Gentile, J.M. (1984). An evaluation of the genotoxic properties of herbicides following plant and animal activation, Mutat. Res., Vol. 136, pp. 233–245.Google Scholar
  10. 10.
    U.S. Environmental Protection Agency (1984). Notice of initiation of special review of regulations of pesticide products containing alachlor, Alachlor Position Document 1, pp. 1–89.Google Scholar
  11. 11.
    Stohs, S.J. (1990). Oxidative Stress induced by 2, 3, 7, 8-tetrachlorodibenzo-pdioxin (TCDD), Free Rad. Biol. Med., Vol. 9, pp. 79–90.Google Scholar
  12. 12.
    Stohs, 5.1 (1995). Synthetic Pro-oxidants: Drugs, Pesticides and other Environmental Pollutants, In Oxidative Stress and Antioxidant Defenses in Biology ( S. Ahmad, Ed.), pp. 117–180. Chapman and Hall, New York.CrossRefGoogle Scholar
  13. 13.
    Sarafian, T. A. and Bredesen, D.E. (1994). Is apoptosis mediated by reactive oxygen species? Free Rad. Res., Vol. 21, pp. 1–8.Google Scholar
  14. 14.
    Naqvi, S.M. and Hasan, M. (1992). Acetylhomocysteine thiolactone protection against phosphamidon-induced alteration of regional superoxide dismutase activity in central nervous system and its correlation with altered lipid peroxidation, Ind. J. Exp. Biol., Vol. 30, pp. 850–852.Google Scholar
  15. 15.
    Yamano, T. and Morita, S. (1992). Hepatotoxicity of trichlorfon and dichlorvos in isolated rat hepatocytes, Toxicol., Vol. 76, pp. 69–77.CrossRefGoogle Scholar
  16. 16.
    Julka, D., Pal, R. and Gill, K.D. (1992). Neurotoxicity of dichlorvos: effect of antioxidant defense system in the rat central nervous system, Exp. Mol. Pathol., Vol. 56, pp. 144–152.PubMedCrossRefGoogle Scholar
  17. 17.
    Akublle, P.I. and Stohs, S.J. (1991). Endrin induced production of nitric oxide by rat peritoneal macrophages, Toxicol. Lett., Vol. 62, pp. 311–316.Google Scholar
  18. 18.
    Sun, Y. (1990). Free Radicals, Antioxidant Enzymes and Carcinogenesis., Free Rad Biol. Med., Vol. 8, pp. 583–589.Google Scholar
  19. 19.
    Halliwell, B., Gutteridge, J.M.C. and Cross, C.E. (1992). Free radicals, antioxidants, and human diseases: where are we now?, J. Lab. Clin. Med., Vol. 119, pp. 598–620.PubMedGoogle Scholar
  20. 20.
    Klaunig, J.E. and Ruch, R.J. (1987). Strain and species effects on the inhibition of hepatocyte intercellular communication by liver tumor promoters, Cancer Lett., Vol, 36, pp. 161–168.Google Scholar
  21. 21.
    Williams, G.M. and Numoto, S. (1984). Promotion of mouse liver neoplasms by the organochlorine pesticides chlordane and hepatochlor in comparison to dichlorodiphenyl trichloroethane, Carcinogenesis, Vol. 5, pp. 1689–1696.PubMedCrossRefGoogle Scholar
  22. 22.
    Lowry, O.H., Rosebrough, N.J., Farr, W.L. and Randall, R.J. (1951). Protein measurement with the fo1in phenol reagent, J. Biol. Chem., Vol. 193, pp. 265275.Google Scholar
  23. 23.
    White, R.D., Sipes, I.G., Gandolfi, A.J. and Bowden, G.T. (1981). Characterization of the hepatic DNA damage caused by I, 2-dibromethane using the alkaline elution technique, Carcinogenesis, Vol. 2, pp. 839–843.PubMedCrossRefGoogle Scholar
  24. 24.
    Buege, J.A. and Aust, S.D. (1972). Microscmal lipid peroxidation, Meth Enzymol., Vol, 51, pp. 302–310.Google Scholar
  25. 25.
    Largilliere, C. and Melàncon, S.B. (1988). Free malondialdehyde determination in human plasma by high-performance liquid chromatography, Analyt. Biochem., Vol, 170, pp. 123–126.Google Scholar
  26. 26.
    Samuni, A., Krishna, M.C., Cook, J., Black, C.D.V. and Russo, A. (1991). On radical production by PMA stimulated neutrophils as monitored by luminolamplified chemiluminescence, Free Rad. Biol. Med., Vol. 10, pp. 313–325.Google Scholar
  27. 27.
    Cederbaum, A.I. and Puntarulo, S. (1988). Comparison of the ability of ferric complexes to catalyze microsomal chemiluminescence, lipid peroxidation and hydroxyl radical generation, Arch, Biochem. Biophys., Vol. 264, pp. 482–491.Google Scholar
  28. 28.
    Bagchi, M., Hassoun, E.A., Bagchi, D. and Stohs, S.J. (1992). Endrin-induced increases in hepatic lipid peroxidation, membrace morcoviscosity, and DNA damage in rats, Arch. Environ. Contam. Toxicol., Vol. 23, pp. 1–5.CrossRefGoogle Scholar
  29. 29.
    Rabich, H., Rosenberg, D.W. and Borenfreund, E. (1991). In vitro cytotoxicity studies with the fish hepatoma cell line, PLHC-1 (Poeciliopsis Incida), Ecotoxicol. Environ, Safety, Vol. 21, pp. 327–336.Google Scholar
  30. 30.
    Lin, M.F., Wu, C.L. and Wang, T.C. (1987). Pesticide clastogenicity in Chinese hamster ovary cells, Mutat. Res., Vol. 188, pp. 241–250.Google Scholar
  31. 31.
    Sharp, D.B. (1988). Alachlor, In Herbicides: Chemistry, Degradation and Mode of Action ( P.C. Kearney and D.D. Kaufman, Eds.) pp. 1–20. Marcel Dekker, New York.Google Scholar
  32. 32.
    Feng, P.C.C. andPatanella, J.E. (1988). Identification of mercapturic acid pathway metabolities of alachlor formed by liver and kidney homogenates of rats, mice and monkeys, Pestic. Biochem. Physiol., Vol. 31, pp. 84–90.CrossRefGoogle Scholar
  33. 33.
    Feng, P.C.C., Wilson, A.G.E., McClanahan, R.H., Patanella, J. E. and Wratten, S.J. (1990). Metabolism of alachlor by rat and mouse liver and nasal turbinate tissues, Drug Metab. Dispos., Vol. 18, pp. 373–377.Google Scholar
  34. 34.
    Kimmel, E.C., Casida, J.E. and Ruzo, L.O. (1986). Formamidine insecticides and chloroacetanilide herbicides: Disubstituted aniline and nitrosobenzenes as mammalian metabolites and bacterial mutagens, J. Agric. Food Chem., Vol. 34, pp. 157–161.CrossRefGoogle Scholar
  35. 35.
    Numan, I.T., Hassan, M.Q. and Stohs, S.J. (1990). Protective effects of antioxidants against endrin-induced lipid peroxidation, glutathione depletion, and lethality in rats, Arch. Environ. Contam. Toxicol., Vol. 19, 302–306.Google Scholar
  36. 36.
    Numan, I.T., Hassan, M.Q. and Stohs, S.J. (1990). Endrin-induced depletion of glutathione and inhibition of glutathione peroxidase activity in rats, Gen. Pharmacol. Vol. 21, pp. 625–628.Google Scholar
  37. 37.
    Hassan, M.Q., Numan, I.T., Al-Nasiro, N. and Stohs, S.J. (1991). Endrin-induced histopathological changes and lipid peroxidation in livers and kidneys of rats, mice guinea pigs and hamsters, Toxicol. Pathol., Vol. 19, pp. 108–114.Google Scholar
  38. 38.
    Bagchi, D., Hassoun, E.A. Bagchi, M. and Stohs, S.J. (1993). Protective effects of antioxidants against endrin-induced hepatic lipid peroxidation, DNA damage, and excretion of urinary lipid metabolites, Free Rad. Biol. Med., Vol. 15, pp. 217–222.Google Scholar
  39. 39.
    Suzaki, E., Inoue, B., Okimasu, E., Ogata, M. and Utsumi, K. (1988). Stimuative effect of chlordane on the various functions of guinea pig leukocytes, toxicol. Appl. Pharmacol., Vol. 93, pp. 137–145.CrossRefGoogle Scholar
  40. 40.
    Rosenstoch, L., Daniell, W., Barnhart, S., Schwartz, D. and Demers, P.A. (1990). Chronic neurophysiological sequelae of occupational exposure to organophosphate insecticides, Am. J. Ind. Med., Vol. 18, pp. 321–325.CrossRefGoogle Scholar
  41. 41.
    Weisenburger, D.D. (1990). Environmental epodemiology of non-Hodgkin’s lymphoma in eastern Neberaska, Am. J. Ind. Med., Vol. 18, pp. 303–305.PubMedCrossRefGoogle Scholar
  42. 42.
    Antunes-Madeira, M.C. and Madeira, V.M.C. (1979). Interaction of insecticides with lipid membranes, Biochim. Biophys. Acta, Vol. 550, pp. 384–392.CrossRefGoogle Scholar
  43. 43.
    Narahashi, T. and Haas, H.G. (1967). DDT: with nerve membrane conductance changes, Science, Vol. 157, pp. 1438–1440.PubMedCrossRefGoogle Scholar
  44. 44.
    Narahashi, T. and Haas, H.G. (1968). Interaction of DDT with the components of lobster nerve membrane conductance, J. Gen. Physiol., Vol. 51, pp. 177–198.PubMedCrossRefGoogle Scholar
  45. 45.
    Matsumura, F, and Patil, K.C. (1969). Adenosine triphosphatase-Sensitive to DDT synapses of rat brain, Science, Vol. 166, pp. 121–122.PubMedCrossRefGoogle Scholar
  46. 46.
    Schneider, R.P. (1975). Mechanism of inhibition of rat brain (Na+K)-adenosine triphosphatase by 2, 2-bis (p-chlorophenyl)-1, 1, 1-trichloroethane (DDT), Biochem. Pharmacol., Vol. 24, pp. 939–946.Google Scholar
  47. 47.
    Bradbury, S.J. (1973). The effect of parathion on crustacean skeletal muscle. I. The mechanical threshold and dependent on Ca+2 ions, Comp. Biochem. Physiol., Vol. 44A, pp. 1021–1032.CrossRefGoogle Scholar
  48. 48.
    Binder, N., Landon, E.J., Weeker, L. and Dettbarn, W.D. (1976). Effect of parathion and its metabolities on Ca+2 uptake activity of rat skeletal muscle sarcoplasmic reticulum in vitro, Biochem. Pharmacol., Vol. 25, pp. 835–839.Google Scholar
  49. 49.
    Domenech, C.E., Machado de Domenech, E.E., Balegno, H.F., de Mendoza, D. and Farias, R.N. (1977). Pesticide action and membrane fluidity, Allosteric behavior of rat erythrocyte membrane-bound acetylcholinesterase in the presence of organophosphorous compounds, FEBS Lett., 74, 243–246.Google Scholar
  50. 50.
    Metcalf, R.L. (1971) In: Pesticides in the Environment, Vol. 1, Part 1 (White-Stevens, R. Ed.), pp. 1–144. Marcel Dekker, Inc., New York.Google Scholar
  51. 51.
    Morrison, H.I., Wilkins, K., Semenciw, R., Mao, Y. and Wigle, D. (1992). Herbicides and Cancer, J. Natl. Can. Inst., Vol. 84, pp. 1866–1874.CrossRefGoogle Scholar
  52. 52.
    Brooks, G.T. (1974). Chlorinated Insecticides: Organic and Biological Chemistry, Chapter IV, pp. 123–231. CRC Press, Cleveland.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • S. J. Stohs
    • 1
  • D. Bagchi
    • 1
  • M. Bagchi
    • 1
  • E. A. Hassoun
    • 1
  1. 1.Department of Pharmaceutical and Administrative SciencesCreighton UniversityOmahaUSA

Personalised recommendations