Effect of glutathione depletion on exocyclic adduct levels in the liver DNA of F344 rats

Raghu G. Nath, Joseph E. Ocando, John Richie, Fung Lung Chung

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The effects of glutathione (GSH) depletion on the in vive formation of cyclic 1,N2-propanodexoxyguanosine adducts (AdG and CdG) as background lesions in the liver DNA of F344 rats were investigated. A group of 5 male F344 rats were given drinking water containing 30 mM L-buthionine (S,R)- sulfoximine (BSO) for 21 days, and another group of 8 rats were given only drinking water as controls. The BSO-treated rats had significantly lower weight gain than control rats. The hepatic GSH levels in the BSO-treated group were reduced by 84% as compared with the control group, from 4.43 to 0.72 μmol/g of tissue. The isomeric AdG3, CdG1, and CdG2 were detected by the 32p-postlabeling/HPLC method in the liver DNA of rats without carcinogen treatment, as we reported previously [Nath, R. G., and Chung, F.- L. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 7491-7495. Nath, R. G., et al. (1996) Cancer Res. 56, 452-456]. The mean levels (μmol/mol of guanine) for AdG3, CdG1, and CdG2 were 0.57 ± 0.25, 0.15 ±0.18, and 0.16 ± 0.22 for the control group and 1.18 ± 1.03, 3.16 ± 3.26, and 2.50 ± 2.59 for the BSO group, respectively. These increases correspond to approximately 2-fold for AdG and 15-21-fold for CdG adducts. The dramatic increase in the cyclic adduct levels in rat liver DNA could have resulted mainly from GSH depletion as a result of the BSO treatment, even though other unknown effects due to the toxicity of BSO cannot be ruled out. These results suggest that GSH plays an important role in protecting the liver against cyclic propano DNA adduction and provide further support for the endogenous origin of these adducts.

Original languageEnglish (US)
Pages (from-to)1250-1253
Number of pages4
JournalChemical research in toxicology
Volume10
Issue number11
DOIs
StatePublished - Dec 22 1997

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Inbred F344 Rats
Liver
Glutathione
Rats
DNA
Drinking Water
Control Groups
Guanine
Carcinogens
Weight Gain
Gain control
High Pressure Liquid Chromatography
Toxicity
Tissue
Neoplasms

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Nath, Raghu G. ; Ocando, Joseph E. ; Richie, John ; Chung, Fung Lung. / Effect of glutathione depletion on exocyclic adduct levels in the liver DNA of F344 rats. In: Chemical research in toxicology. 1997 ; Vol. 10, No. 11. pp. 1250-1253.
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title = "Effect of glutathione depletion on exocyclic adduct levels in the liver DNA of F344 rats",
abstract = "The effects of glutathione (GSH) depletion on the in vive formation of cyclic 1,N2-propanodexoxyguanosine adducts (AdG and CdG) as background lesions in the liver DNA of F344 rats were investigated. A group of 5 male F344 rats were given drinking water containing 30 mM L-buthionine (S,R)- sulfoximine (BSO) for 21 days, and another group of 8 rats were given only drinking water as controls. The BSO-treated rats had significantly lower weight gain than control rats. The hepatic GSH levels in the BSO-treated group were reduced by 84{\%} as compared with the control group, from 4.43 to 0.72 μmol/g of tissue. The isomeric AdG3, CdG1, and CdG2 were detected by the 32p-postlabeling/HPLC method in the liver DNA of rats without carcinogen treatment, as we reported previously [Nath, R. G., and Chung, F.- L. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 7491-7495. Nath, R. G., et al. (1996) Cancer Res. 56, 452-456]. The mean levels (μmol/mol of guanine) for AdG3, CdG1, and CdG2 were 0.57 ± 0.25, 0.15 ±0.18, and 0.16 ± 0.22 for the control group and 1.18 ± 1.03, 3.16 ± 3.26, and 2.50 ± 2.59 for the BSO group, respectively. These increases correspond to approximately 2-fold for AdG and 15-21-fold for CdG adducts. The dramatic increase in the cyclic adduct levels in rat liver DNA could have resulted mainly from GSH depletion as a result of the BSO treatment, even though other unknown effects due to the toxicity of BSO cannot be ruled out. These results suggest that GSH plays an important role in protecting the liver against cyclic propano DNA adduction and provide further support for the endogenous origin of these adducts.",
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Effect of glutathione depletion on exocyclic adduct levels in the liver DNA of F344 rats. / Nath, Raghu G.; Ocando, Joseph E.; Richie, John; Chung, Fung Lung.

In: Chemical research in toxicology, Vol. 10, No. 11, 22.12.1997, p. 1250-1253.

Research output: Contribution to journalArticle

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T1 - Effect of glutathione depletion on exocyclic adduct levels in the liver DNA of F344 rats

AU - Nath, Raghu G.

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N2 - The effects of glutathione (GSH) depletion on the in vive formation of cyclic 1,N2-propanodexoxyguanosine adducts (AdG and CdG) as background lesions in the liver DNA of F344 rats were investigated. A group of 5 male F344 rats were given drinking water containing 30 mM L-buthionine (S,R)- sulfoximine (BSO) for 21 days, and another group of 8 rats were given only drinking water as controls. The BSO-treated rats had significantly lower weight gain than control rats. The hepatic GSH levels in the BSO-treated group were reduced by 84% as compared with the control group, from 4.43 to 0.72 μmol/g of tissue. The isomeric AdG3, CdG1, and CdG2 were detected by the 32p-postlabeling/HPLC method in the liver DNA of rats without carcinogen treatment, as we reported previously [Nath, R. G., and Chung, F.- L. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 7491-7495. Nath, R. G., et al. (1996) Cancer Res. 56, 452-456]. The mean levels (μmol/mol of guanine) for AdG3, CdG1, and CdG2 were 0.57 ± 0.25, 0.15 ±0.18, and 0.16 ± 0.22 for the control group and 1.18 ± 1.03, 3.16 ± 3.26, and 2.50 ± 2.59 for the BSO group, respectively. These increases correspond to approximately 2-fold for AdG and 15-21-fold for CdG adducts. The dramatic increase in the cyclic adduct levels in rat liver DNA could have resulted mainly from GSH depletion as a result of the BSO treatment, even though other unknown effects due to the toxicity of BSO cannot be ruled out. These results suggest that GSH plays an important role in protecting the liver against cyclic propano DNA adduction and provide further support for the endogenous origin of these adducts.

AB - The effects of glutathione (GSH) depletion on the in vive formation of cyclic 1,N2-propanodexoxyguanosine adducts (AdG and CdG) as background lesions in the liver DNA of F344 rats were investigated. A group of 5 male F344 rats were given drinking water containing 30 mM L-buthionine (S,R)- sulfoximine (BSO) for 21 days, and another group of 8 rats were given only drinking water as controls. The BSO-treated rats had significantly lower weight gain than control rats. The hepatic GSH levels in the BSO-treated group were reduced by 84% as compared with the control group, from 4.43 to 0.72 μmol/g of tissue. The isomeric AdG3, CdG1, and CdG2 were detected by the 32p-postlabeling/HPLC method in the liver DNA of rats without carcinogen treatment, as we reported previously [Nath, R. G., and Chung, F.- L. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 7491-7495. Nath, R. G., et al. (1996) Cancer Res. 56, 452-456]. The mean levels (μmol/mol of guanine) for AdG3, CdG1, and CdG2 were 0.57 ± 0.25, 0.15 ±0.18, and 0.16 ± 0.22 for the control group and 1.18 ± 1.03, 3.16 ± 3.26, and 2.50 ± 2.59 for the BSO group, respectively. These increases correspond to approximately 2-fold for AdG and 15-21-fold for CdG adducts. The dramatic increase in the cyclic adduct levels in rat liver DNA could have resulted mainly from GSH depletion as a result of the BSO treatment, even though other unknown effects due to the toxicity of BSO cannot be ruled out. These results suggest that GSH plays an important role in protecting the liver against cyclic propano DNA adduction and provide further support for the endogenous origin of these adducts.

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