Effect of bromine and chlorine positioning in the induction of renal and testicular toxicity by halogenated propanes.
Effect of bromine and chlorine positioning in the induction of renal and testicular toxicity by halogenated propanes.
复制标题
溴和氯定位对卤化丙烷诱导肾和睾丸毒性的影响。
DOI：
10.1021/tx00023a007
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发表时间：
1991
影响因子：
4.1
通讯作者：
Dybing,E
中科院分区：
文献类型：
--
作者：
Låg,M;Søderlund,EJ;Omichinski,JG;Brunborg,G;Holme,JA;Dahl,JE;Nelson,SD;Dybing,E
研究了一系列卤代丙烷对大鼠肾脏和睾丸的致坏死作用，并与其诱导体内肾脏和睾丸DNA损伤和体外睾丸DNA损伤的能力相关。1，2-二溴-3-氯丙烷（DBCP）和1，2，3-三溴丙烷对肾脏和睾丸的损伤作用最强。在85 μ mol/kg时肾脏和170 μ mol/kg时睾丸出现广泛坏死。二溴一氯类似物1，3-二溴-2-氯丙烷的器官毒性低于DBCP和1，2，3-三溴丙烷，但引起的器官损害高于二氯一溴类似物1-溴-2，3-二氯丙烷和1，3-二氯-2-溴丙烷。二卤代丙烷的致坏死性更小。这些观察到的卤代丙烷之间的毒性差异不能用组织浓度的相对差异来解释。卤代丙烷在体内诱导DNA损伤的能力与其诱导器官损伤的能力密切相关。然而，与器官坏死相比，DNA损伤发生在较低剂量和较短暴露时间内。这表明DNA损伤可能是卤代丙烷引起器官坏死的初始事件。此外，卤代丙烷在体内诱导的睾丸DNA损伤与在体外分离的睾丸细胞中观察到的DNA损伤密切相关，表明毒性是由于原位激活。卤素取代基的数量、位置和类型似乎是导致DNA损伤和坏死效应的重要决定因素。卤代丙烷的潜在毒性顺序为：1，2，3-三溴丙烷> 1，2-二溴-3-氯丙烷> 1，3-二溴-2-氯丙烷> 1，3-二氯-2-溴丙烷; 1-溴-2，3-二氯丙烷> 1，2，3-三氯丙烷=* 1，2-二溴丙烷> 1，3-二溴丙烷> 1-溴-3-氯丙烷。毒性最大的类似物含有三个卤素，至少有两个连位溴。
A series of halogenated propanes were studied for renal and testicular necrogenic effects in the rat and correlated to their ability to induce in vivo renaland testicular DNA damage and in vitro testicular DNA damage. l, 2-Dibromo-3-chloropropane (DBCP) and 1, 2, 3-tribromopropane were most potent in causing organ damage in both kidney and testes. Extensive necrosis was evident at 85/rmol/kg in kidneyand at 170 jtmol/kg in testis. The dibromomonochlorinated analogue l, 3-dibromo-2-chloropropane was less organ toxic than DBCP and 1, 2, 3-tribromopropane, but induced more organ damage than the dichloromonobrominated analogues 1-bromo-2, 3-dichloropropane and l, 3-dichloro-2-bromopropane. Dihalogenated propanes were even less necrogenic. These observed differences in toxic potencybetween the halogenated propanes could not be explained by relative differences in tissue concentrations. The ability of the halogenatedpropanes to induce DNA damage in vivo correlated well with their ability to induce organdamage. However, DNA damage occurred at lower doses and at a shorter period of exposure than organ necrosis. This indicates that DNA damage might be an initial event in the development of organ necrosis by halogenated propanes in general. Further, testicular DNA damage inducedby the halogenated propanes in vivo correlated well with the DNA damage observed in isolated testicular cells in vitro, showing that toxicity was due to in situ activation. The numbers, positions, and the types of halogen substituents appear to be important determinants in causing DNA damage and necrogenic effects. The toxic potential of the halogenated propanes was in the following order: 1, 2, 3-tribromopropane> l, 2-dibromo-3-chloropropane> l, 3-dibromo-2-chloropropane> l, 3-dichloro-2-bromopropane a; l-bromo-2, 3-dichloropropane> 1, 2, 3-trichloropropane=* 1, 2-dibromopropane> 1, 3-dibromopropane> l-bromo-3-chloro-propane. The most toxic analogues contain three halogens with at least two vicinal bromines.