Genotoxicity of styrene-7,8-oxide and styrene in Fisher 344 rats: A 4-week inhalation study
- 作者：Laurent Gaté ; ; Laurent.gate@inrs.fr ; Jean-Claude Micillino ; Sylvie Sé ; billaud ; Cristina Langlais ; Fré ; dé ; ric Cosnier ; Hervé ; Nunge ; Christian Darne ; Yves Guichard ; Sté ; phane Binet
- 关键词：PBPK ; physiologically-based pharmacokinetic ; SO ; styrene-7 ; 8-oxide ; ENU ; N-ethyl-N-nitrosourea ; Fpg ; formamidopyrimidine DNA glycosylase ; Gr ; granulocyte ; ACGIH ; American Conference of Governmental Industrial Hygienists
- 刊名：Toxicology Letters
- 出版年：2012
- 期刊代码：49_03784274
- 类别：pha
- 出版时间：20 June, 2012
- 卷：211
- 期：3
- 页码：211-219
- 文件大小：465 K
摘要
The cytogenetic alterations in leukocytes and the increased risk for leukemia, lymphoma, or all lymphohematopoietic cancer observed in workers occupationally exposed to styrene have been associated with its hepatic metabolisation into styrene-7,8-oxide, an epoxide which can induce DNA damages. However, it has been observed that styrene-7,8-oxide was also found in the atmosphere of reinforced plastic industries where large amounts of styrene are used. Since the main route of exposure to these compounds is inhalation, in order to gain new insights regarding their systemic genotoxicity, Fisher 344 male rats were exposed in full-body inhalation chambers, 6 h/day, 5 days/week for 4 weeks to styrene-7,8-oxide (25, 50, and 75 ppm) or styrene (75, 300, and 1000 ppm). Then, the induction of micronuclei in circulating reticulocytes and DNA strand breaks in leukocytes using the comet assay was studied at the end of the 3rd and 20th days of exposure. Our results showed that neither styrene nor styrene-7,8-oxide induced a significant increase of the micronucleus frequency in reticulocytes or DNA strand breaks in white blood cells. However, in the presence of the formamidopyridine DNA glycosylase, an enzyme able to recognize and excise DNA at the level of some oxidized DNA bases, a significant increase of DNA damages was observed at the end of the 3rd day of treatment in leukocytes from rats exposed to styrene but not to styrene-7,8-oxide. This experimental design helped to gather new information regarding the systemic genotoxicity of these two chemicals and may be valuable for the risk assessment associated with an occupational exposure to these molecules.