Intra- and Inter-Species Variability in Urinary N7-(1-Hydroxy-3-buten-2-yl)guanine Adducts Following Inhalation Exposure to 1,3-Butadiene.
Intra- and Inter-Species Variability in Urinary N7-(1-Hydroxy-3-buten-2-yl)guanine Adducts Following Inhalation Exposure to 1,3-Butadiene.
复制标题
DOI：
10.1021/acs.chemrestox.1c00291
复制
发表时间：
2021-11-15
影响因子：
4.1
通讯作者：
Rusyn I
中科院分区：
文献类型：
--
作者：
Erber L;Goodman S;Wright FA;Chiu WA;Tretyakova NY;Rusyn I
1,3-Butadiene is a known carcinogen primarily targeting lymphoid tissues, lung, and liver. Cytochrome P450 activates butadiene to epoxides which form covalent DNA adducts that are thought to be a key mechanistic event in cancer. Previous studies suggested that inter-species, -tissue, and -individual susceptibility to adverse health effects of butadiene exposure may be due to differences in metabolism, as well as other mechanisms. In this study, we aimed to examine the extent of inter-individual and inter-species variability in urinary N7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) DNA adducts, a well-known biomarker of exposure to butadiene. For a population variability study in mice, we used the Collaborative Cross model. Female and male mice from 5 strains were exposed to filtered air or butadiene (590 ppm, 6 h/day, 5 days/week for 2 weeks) by inhalation. Urine samples were collected, and the metabolic activation of butadiene to DNA-reactive species was quantified as urinary EB-GII adducts. We quantified the degree of EB-GII variation across mouse strains and sexes; then, we compared this variation with the data from rats (exposed to 62.5 or 200 ppm butadiene) and humans (0.004-2.2 ppm butadiene). We show that sex and strain are significant contributors to the variability in urinary EB-GII levels in mice. In addition, we find that the degree of variability in urinary EB-GII in Collaborative Cross mice, when expressed as uncertainty factor for the inter-individual variability (UFH), is relatively modest (≤ 3-fold), possibly due to metabolic saturation. By contrast, variability in urinary EB-GII (adjusted for exposure) observed in humans, while larger than the default value of 10-fold, is largely consistent with UFH estimates for other chemicals based on human data for non-cancer endpoints. Overall, these data demonstrate that urinary EB-GII levels, particularly from human studies, may be useful for quantitative characterization of human variability in the cancer risks to butadiene.
登录
查看更多内容
DOI：
10.1016/j.mrgentox.2009.05.006
发表时间：
2009-08
影响因子：
1.9
作者：
Boysen, Gunnar;Pachkowski, Brian F.;Nakamura, Jun;Swenberg, James A.
通讯作者：
Swenberg, James A.
影响因子：
4.7
作者：
COCHRANE, JE;SKOPEK, TR
通讯作者：
SKOPEK, TR
影响因子：
10.4
作者：
FAJEN, JM;ROBERTS, DR;KRISHNAN, ER
通讯作者：
KRISHNAN, ER
影响因子：
4.1
作者：
Goggin, Melissa;Anderson, Chris;Tretyakova, Natalia
通讯作者：
Tretyakova, Natalia
影响因子：
5.1
作者：
Boysen, Gunnar;Georgieva, Nadia I.;Swenberg, James A.
通讯作者：
Swenberg, James A.