Testicular necrosis and DNA damage caused by deuterated and methylated analogs of 1,2-dibromo-3-chloropropane in the rat.
Testicular necrosis and DNA damage caused by deuterated and methylated analogs of 1,2-dibromo-3-chloropropane in the rat.
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1,2-二溴-3-氯丙烷的氘化和甲基化类似物在大鼠体内引起睾丸坏死和 DNA 损伤。
DOI：
10.1016/0041-008x(88)90284-0
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发表时间：
1988
影响因子：
3.8
通讯作者：
Dybing,E
中科院分区：
文献类型：
--
作者：
Søderlund,EJ;Brunborg,G;Omichinski,JG;Holme,JA;Dahl,JE;Nelson,SD;Dybing,E
为了研究代谢在1，2-二溴-3-氯丙烷（DBCP）诱导的大鼠睾丸损伤中的作用，选择性地以340 μmol/kg剂量单次ip给予DBCP的氘代和甲基化类似物，并在处理后10天测定睾丸毒性。与DBCP相比，四种氘代类似物C1-D2-、C2-D1-、C3-D2-或C1-C2-C3-D5-DBCP均未降低睾丸损伤程度，表明C-OH键的代谢裂解在DBCP诱导的睾丸毒性中不是限速的。在5种甲基化类似物（C1-甲基-、C1-二甲基-、C2-甲基-和C3-甲基-DBCP和1，2-二溴-4-氯丁烷）中，仅C3-甲基-DBCP引起睾丸毒性。在85-170 μmol/kg剂量下，DBCP处理导致睾丸DNA损伤增加，通过体内处理后3小时分离的睾丸细胞中DNA的碱性洗脱进行测量。全氘代-DBCP类似物诱导睾丸DNA损伤，其至少与DBCP诱导的损伤一样广泛。在测试的甲基化类似物中，仅C3-甲基-DBCP在170和540 μmol/kg之间引起睾丸DNA损伤的显著剂量依赖性增加。DBCP、全氘代DBCP和甲基化DBCP类似物之间的睾丸组织分布没有显著差异。此外，在对二溴氯丙烷、C1-甲基-和C3-甲基-二溴氯丙烷以及1，2-二溴-4-氯丁烷的分布研究中，发现肾脏中的组织浓度最高，其次是肝脏，然后是睾丸。DBCP及其氘代和甲基化类似物的睾丸DNA损伤证明了它们导致睾丸坏死和萎缩的能力，这一事实使得DNA损伤的测量在DBCP诱导的睾丸细胞死亡的机制研究中成为非常有用的相关因素。
To study the role of metabolism in 1,2-dibromo-3-chloropropane (DBCP)-induced testicular damage in rats, selectively deuterated and methylated analogs of DBCP were given as a single ip dose of 340 μmol/kg and testicular toxicity was determined 10 days after treatment. None of the four deuterated analogs C1-D2-, C2-D1-, C3-D2-, or C1-C2-C3-D5-DBCP reduced the degree of testicular damage compared to DBCP, indicating that metabolic cleavage of a CH bond was not rate-limiting in DBCP-induced testicular toxicity. Of the five methylated analogs, C1-methyl-, C1-dimethyl-, C2-methyl-, and C3-methyl-DBCP and 1,2-dibromo-4-chlorobutane, only C3-methyl-DBCP caused testicular toxicity. DBCP treatment resulted in increased testicular DNA damage at doses of 85–170 μmol/kg as measured by alkaline elution of DNA from testicular cells isolated 3 hr after in vivo treatment. The perdeutero-DBCP analog induced testicular DNA damage that was at least as extensive as that induced by DBCP. Of the methylated analogs tested, only C3-methyl-DBCP gave a marked dose-dependent increase in testicular DNA damage between 170 and 540 μmol/kg. There were no significant differences in the testicular tissue distribution between DBCP, perdeutero-DBCP, and the methylated DBCP analogs. Furthermore, in distribution studies with DBCP, C1-methyl- and C3-methyl-DBCP, and 1,2-dibromo-4-chlorobutane, the highest tissue concentrations were found in the kidneys, followed by the liver and then the testes. The fact that testicular DNA damage of DBCP and its deuterated and methylated analogs paralleled their ability to cause testicular necrosis and atrophy makes measurement of DNA damage a very useful correlate in mechanistic studies of DBCP-induced testicular cell death.
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影响因子：
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作者：
Robert D. Short;Robert D. Short;Joseph M. Winston;Joseph M. Winston;Chuen;Chuen;Jan L. Minor;Jan L. Minor;Cheng;Cheng;Joseph Seifter;Joseph Seifter
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DOI：
--
发表时间：
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期刊：
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影响因子：
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作者：
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影响因子：
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作者：
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作者：
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