Gender differences in the metabolism of 1,3-butadiene in Sprague-Dawley rats following a low level inhalation exposure.
Gender differences in the metabolism of 1,3-butadiene in Sprague-Dawley rats following a low level inhalation exposure.
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低水平吸入暴露后 Sprague-Dawley 大鼠 1,3-丁二烯代谢的性别差异。
DOI：
10.1093/carcin/16.11.2875
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发表时间：
1995
期刊：
影响因子：
4.7
通讯作者：
R. Henderson
中科院分区：
文献类型：
--
作者：
J. Thornton;A. Dahl;W. Bechtold;W. Griffith;L. Pei;R. Henderson
1，3-丁二烯(BD)是一种在橡胶工业中广泛使用的化合物，在慢性暴露于1000和8000 p.pm后，对雄性和雌性Spraogue-Dawley大鼠具有致癌作用。就肿瘤的发病率而言，大多数发生在乳腺组织，因此在慢性致癌性研究中，雌性大鼠的肿瘤发病率高于雄性大鼠。本文研究了BD致突变代谢产物丁二烯单环氧化物(BDO)和丁二烯二环氧化物(BDO2)在低水平吸入BD后的产生和处置。这些大鼠暴露在目标浓度为62.5 ppm的环境中。染毒后即刻取血、骨髓、肺和脂肪标本，取雌鼠乳房组织。采用低温-减压线蒸馏法制备了样品，并用多维气相色谱-质谱仪对样品中的环氧化物进行分析。血中BDO水平男性为25.9+/-2.9，女性为29.4+/-2pmol/g。在被检查的其他组织中，雄性和雌性的这种代谢物的水平也是相似的。脂肪中的BDO含量最高，男性为175+/-21，女性为203+/-13pmol/g。雌性大鼠血液中的BDO2水平大约是雄性大鼠的5倍。在被检查的其他组织中，BDO2在女性组织中的含量也一直较高。在脂肪中，BDO2在雌性和雄性组织中的浓度分别为7.7+/-1.3和1.1+/-0.1pmol/g组织。雌性大鼠乳腺组织中BDO2的含量为10.5+/-2.4pmol/g，略低于血液中观察到的水平。在所检查的所有组织中，这两种环氧化物的比例在雄性和雌性之间存在显著差异。差异在肺和脂肪组织中最为明显，男性和女性的BDO/BDO2比率分别为9和0.6(肺部)和159和26(脂肪)。这项研究首次描述了BD代谢的性别差异。女性体内高诱变性BDO2的大量产生可能是长期接触BD后乳腺癌发病率增加的原因之一。
1,3-Butadiene (BD), a compound used extensively in the rubber industry, is carcinogenic in the male and female Sprague-Dawley rats after chronic exposures to 1000 and 8000 p.p.m. In terms of incidence of tumors the majority were in mammary tissue, thus the incidence of tumors in female rats exceeded that in males in chronic carcinogenicity studies. In the present study the production and disposition of butadiene monoepoxide (BDO) and butadiene diepoxide (BDO2), mutagenic BD metabolites, were examined in male and female Sprague-Dawley rats following a low level inhalation exposure to BD. The rats were exposed to a target concentration of 62.5 p.p.m. BD by nasal inhalation for 6 h. Immediately after exposure blood, bone marrow, lung and fat samples were removed from all the animals and mammary tissue was removed from females. The samples were prepared by cryogenic-vacuum line distillation and analyzed for the epoxides using multidimensional gas chromatography-mass spectrometry. Levels of BDO in the blood were 25.9 +/- 2.9 and 29.4 +/- 2 pmol/g in male and females respectively. The levels of this metabolite were also similar in males and females in the other tissues examined. The greatest amounts of BDO were in fat (175 +/- 21 and 203 +/- 13 pmol/g in males and females respectively). Levels of BDO2 were approximately 5-fold greater in the blood of female rats compared with male rats. In the other tissues examined BDO2 was also consistently greater in tissues from females. In fat BDO2 was present at a concentration of 7.7 +/- 1.3 and 1.1 +/- 0.1 pmol/g tissue in females and males respectively. Mammary tissue from female rats contained 10.5 +/- 2.4 pmol/g BDO2, a level slightly lower than that observed in blood. The ratios of the two epoxides differed markedly between males and females in all tissues examined. Differences were most pronounced in lung and fat tissues, where BDO/BDO2 ratios were 9 and 0.6 (lung) and 159 and 26 (fat) for males and females respectively. This study is the first to describe a gender difference in the metabolism of BD. The greater production of the highly mutagenic BDO2 in females may play a role in the increased incidence of mammary tumors after chronic exposure to BD.