The role of glutathione S-transferase genes in the susceptibility to genetic damage in humans and rodents

详细信息    查看全文

• 作者：Kligerman ; Andrew ; DeMarini ; David ; Doerr ; Carolyn ; Hanley ; Nancy ; Milholland ; Velva ; Tennant ; Alan
• 关键词：glutathione S-transferase ; butadiene ; SCEs
• 刊名：Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
• 出版年：1997
• 出版时间：September, 1997
• 年：1997
• 卷：379
• 期：1, Supplement 1
• 页码：S10
• 全文大小：122 K

文摘

To understand better the species differences in carcinogenicity induced by 1,3-butadiene (BD), we exposed splenic and peripheral blood lymphocytes from rats, mice, and humans to 3,4-epoxy-1-butene (EB) or 1,2:3,4-diepoxybutane (DEB). These studies indicate that EB does not induce measurable cytogenetic damage in either rat or mouse G<sub>0sub> splenocytes as measured by either sister chromatid exchange (SCE) or chromosome aberration (CA) analyses. However, DEB was a potent inducer of both SCEs and CAs in G<sub>0sub> splenic and peripheral blood lymphocytes. A comparison of the responses among species showed that the rat and mouse were approximately equisensitive to the cytogenetic damaging effects of DEB, but the situation for the human subjects was more complex. The presence or absence of the GSTT1 gene (expressed in erythrocytes) determined the relative sensitivity of the PBLs to the cytogenetic damaging effects of DEB. EB was a moderately potent SCE-inducer when administered to actively dividing cells during the last 24 h of culture in all three species. However, DEB was > 10x more potent than EB for SCE induction. Similar to what was found with DEB, GSTM1 had no effect on the sensitivity to EB, whereas the lack of GSTT1 markedly increased the cells' sensitivity to EB. Studies underway are examining rodents for increased susceptibility to EB and DEB due to variations in the rodent homologs of GSTT1 and GSTM1 genes. (This abstract does not necessarily reflect EPA policy).