Abstract
Chemicals combine with DNA, resulting in DNA damage, which could initiate carcinogenesis. To study whether benzene or benzene metabolites bind to DNA, DNA adducts in various tissues and their persistence in leukocytes were examined using the 32P-postlabeling assay. LACA mice were dosed ip with benzene at 500 mg/kg bw twice for 5 days. Two additional spots of DNA adducts are formed in bone marrow cells, liver cells, and peripheral blood compared with control mice. The relative adduct labeling values are 10.39, 11.32, and 13.77 adducts x 10(-8) nucleotides in these tissues, respectively. DNA adducts in blood leukocytes were observed at 1, 4, 7, 14, and 21 days after exposure to benzene, but adduct levels decreased as a function of time. Relative adduct labeling of "adduct B" declined linearly but mildly, while "adduct C" displayed a stepwise decrease. The relative adduct labeling values of both these adducts at day 14 were 50% of those at day 1 after the last treatment. Both adducts were still detectable at day 21 after benzene exposure. These studies demonstrate that benzene could induce DNA adducts in bone marrow, liver, and white blood cells of mice dosed with benzene and that measurement of adducts in white blood cells may be useful as a biomarker to predict carcinogenic risk of benzene to workers exposed to benzene.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bauer H., Dimitriadis E. A., Snyder R. An in vivo study of benzene metabolite DNA adduct formation in liver of male New Zealand rabbits. Arch Toxicol. 1989;63(3):209–213. doi: 10.1007/BF00316370. [DOI] [PubMed] [Google Scholar]
- Krewet E., Verkoyen C., Müller G., Schell C., Popp W., Norpoth K. Studies on guanine adducts excreted in rat urine after benzene exposure. Carcinogenesis. 1993 Feb;14(2):245–250. doi: 10.1093/carcin/14.2.245. [DOI] [PubMed] [Google Scholar]
- Miller E. C., Miller J. A. Mechanisms of chemical carcinogenesis. Cancer. 1981 Mar 1;47(5 Suppl):1055–1064. doi: 10.1002/1097-0142(19810301)47:5+<1055::aid-cncr2820471302>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
- Reddy M. V., Blackburn G. R., Schreiner C. A., Mehlman M. A., Mackerer C. R. 32P analysis of DNA adducts in tissues of benzene-treated rats. Environ Health Perspect. 1989 Jul;82:253–257. doi: 10.1289/ehp.8982253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reddy M. V., Randerath K. Nuclease P1-mediated enhancement of sensitivity of 32P-postlabeling test for structurally diverse DNA adducts. Carcinogenesis. 1986 Sep;7(9):1543–1551. doi: 10.1093/carcin/7.9.1543. [DOI] [PubMed] [Google Scholar]
- Snyder R., Dimitriadis E., Guy R., Hu P., Cooper K., Bauer H., Witz G., Goldstein B. D. Studies on the mechanism of benzene toxicity. Environ Health Perspect. 1989 Jul;82:31–35. doi: 10.1289/ehp.898231. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yin S. N., Li Q., Liu Y., Tian F., Du C., Jin C. Occupational exposure to benzene in China. Br J Ind Med. 1987 Mar;44(3):192–195. doi: 10.1136/oem.44.3.192. [DOI] [PMC free article] [PubMed] [Google Scholar]