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Induction of oxidative stress in rat brain by acrylonitrile (ACN).
Toxicol Sci. 1998 Dec; 46(2):333-41.TS

Abstract

Chronic treatment with acrylonitrile (ACN) has been shown to produce a dose-related increase in glial cell tumors (astrocytomas) in rats. The mechanism(s) for ACN-induced carcinogenicity remains unclear. While ACN has been reported to induce DNA damage in a number of short-term systems, evidence for a genotoxic mechanism of tumor induction is the brain is not strong. Other toxic mechanisms appear to participate in the induction of tumor or induce the astrocytomas solely. In particular, nongenotoxic mechanisms of carcinogen induction have been implicated in this ACN-induced carcinogenic effect in the rat brain. One major pathway of ACN metabolism is through glutathione (GSH) conjugation. Extensive utilization and depletion of GSH, an important intracellular antioxidant, by ACN may lead to cellular oxidative stress. The present study examined the ability of ACN to induce oxidative stress in male Sprague-Dawley rats. Rats were administered ACN at concentrations of 0, 5, 10, 100, or 200 ppm in the drinking water and sampled after 14, 28, or 90 days of continuous treatment. Oxidative DNA damage indicated by the presence of 8-hydroxy-2'-deoxyguanosine (OH8dG) and lipid peroxidation indicated by the presence of malondialdehyde (MDA), a lipid peroxidation product, in rat brains and livers were examined. The levels of reactive oxygen species (ROS) were also determined in different rat tissues. Both the levels of nonenzymatic antioxidants (GSH, vitamin E) and the activities of enzymatic antioxidants (catalase, superoxide dismutase, glutathione peroxidase) in rat brains and livers were measured. Increased levels of OH8dG, MDA, and ROS were found in the brains of ACN-treated rats. Decreased levels of GSH and activities of catalase and SOD were also observed in the brains of ACN-treated rats compared to the control group. Interestingly, there were no changes of these indicators of oxidative stress in the livers of ACN-treated rats. Rat liver is not a target for ACN-induced carcinogenesis. These data indicate that ACN selectively induces oxidative stress in rat brain at doses that produce carcinogenesis in chronic treatment studies.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10048137

Citation

Jiang, J, et al. "Induction of Oxidative Stress in Rat Brain By Acrylonitrile (ACN)." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 46, no. 2, 1998, pp. 333-41.
Jiang J, Xu Y, Klaunig JE. Induction of oxidative stress in rat brain by acrylonitrile (ACN). Toxicol Sci. 1998;46(2):333-41.
Jiang, J., Xu, Y., & Klaunig, J. E. (1998). Induction of oxidative stress in rat brain by acrylonitrile (ACN). Toxicological Sciences : an Official Journal of the Society of Toxicology, 46(2), 333-41.
Jiang J, Xu Y, Klaunig JE. Induction of Oxidative Stress in Rat Brain By Acrylonitrile (ACN). Toxicol Sci. 1998;46(2):333-41. PubMed PMID: 10048137.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of oxidative stress in rat brain by acrylonitrile (ACN). AU - Jiang,J, AU - Xu,Y, AU - Klaunig,J E, PY - 1999/2/27/pubmed PY - 1999/2/27/medline PY - 1999/2/27/entrez SP - 333 EP - 41 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol Sci VL - 46 IS - 2 N2 - Chronic treatment with acrylonitrile (ACN) has been shown to produce a dose-related increase in glial cell tumors (astrocytomas) in rats. The mechanism(s) for ACN-induced carcinogenicity remains unclear. While ACN has been reported to induce DNA damage in a number of short-term systems, evidence for a genotoxic mechanism of tumor induction is the brain is not strong. Other toxic mechanisms appear to participate in the induction of tumor or induce the astrocytomas solely. In particular, nongenotoxic mechanisms of carcinogen induction have been implicated in this ACN-induced carcinogenic effect in the rat brain. One major pathway of ACN metabolism is through glutathione (GSH) conjugation. Extensive utilization and depletion of GSH, an important intracellular antioxidant, by ACN may lead to cellular oxidative stress. The present study examined the ability of ACN to induce oxidative stress in male Sprague-Dawley rats. Rats were administered ACN at concentrations of 0, 5, 10, 100, or 200 ppm in the drinking water and sampled after 14, 28, or 90 days of continuous treatment. Oxidative DNA damage indicated by the presence of 8-hydroxy-2'-deoxyguanosine (OH8dG) and lipid peroxidation indicated by the presence of malondialdehyde (MDA), a lipid peroxidation product, in rat brains and livers were examined. The levels of reactive oxygen species (ROS) were also determined in different rat tissues. Both the levels of nonenzymatic antioxidants (GSH, vitamin E) and the activities of enzymatic antioxidants (catalase, superoxide dismutase, glutathione peroxidase) in rat brains and livers were measured. Increased levels of OH8dG, MDA, and ROS were found in the brains of ACN-treated rats. Decreased levels of GSH and activities of catalase and SOD were also observed in the brains of ACN-treated rats compared to the control group. Interestingly, there were no changes of these indicators of oxidative stress in the livers of ACN-treated rats. Rat liver is not a target for ACN-induced carcinogenesis. These data indicate that ACN selectively induces oxidative stress in rat brain at doses that produce carcinogenesis in chronic treatment studies. SN - 1096-6080 UR - https://www.unboundmedicine.com/medline/citation/10048137/Induction_of_oxidative_stress_in_rat_brain_by_acrylonitrile__ACN__ L2 - https://academic.oup.com/toxsci/article-lookup/doi/10.1006/toxs.1998.2524 DB - PRIME DP - Unbound Medicine ER -