Formation of DNA adducts and oxidative DNA damage in rats treated with 1,6-dinitropyrene
| Autor: | Zora Djuric, S.J. Culp, Frederick A. Beland, David W. Potter, Domenico A. Luongo |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Cancer Research
DNA damage medicine.medical_treatment Urinary Bladder Intraperitoneal injection Rats Sprague-Dawley chemistry.chemical_compound In vivo medicine Animals Carcinogen Pyrenes Chemistry Deoxyguanosine 8-Hydroxy-2'-deoxyguanosine DNA Rats Liver Oncology Biochemistry 8-Hydroxy-2'-Deoxyguanosine Toxicity Female Oxidation-Reduction Nucleoside DNA Damage Thymidine |
| Zdroj: | Cancer Letters. 71:51-56 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/0304-3835(93)90096-r |
| Popis: | In vitro metabolism studies have indicated that the tumorigenic environmental pollutant 1,6-dinitropyrene has the potential to bind covalently to DNA and to induce oxidative DNA damage. We have determined if 1,6-dinitropyrene treatment will cause both types of DNA damage in vivo. Female Sprague-Dawley rats were given a single intraperitoneal injection of 1,6-dinitropyrene, and covalent DNA adduct formation, as indicated by the presence of N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene, and oxidative DNA damage, as indicated by increases in 5-hydroxymethyl-2′-deoxyuridine and 8-hydroxy-2′-deoxyguanosine, were assessed at 3, 12, 24 and 48 h after dosing. 32P-postlabeling analyses of DNA isolated from liver, mammary gland, bladder and nucleated blood cells indicated the formation of N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene, with the levels being highest in the bladder. 5-hydroxy-methyl-2′-deoxyuridine was detected in DNA from each of these tissues, and the levels of this oxidized nucleoside were higher in the mammary glands and livers of 1,6-dinitropyrene-treated rats. 1,6-Dinitropyrene dosing did not affect the levels of 8-hydroxy-2′-deoxyguanosine in these two tissues. These results indicate that exposure to 1,6-dinitropyrene can result in increased levels of 5-hydroxymethyl-2′-deoxyuridine in addition to covalent DNA adduct formation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|