Holme J A, Søderlund E J, Hongslo J K, Nelson S D, Dybing E
Mutat Res. 1983 Dec;124(3-4):213-24. doi: 10.1016/0165-1218(83)90192-1.
Tris(2,3-dibromopropyl)phosphate (Tris-BP) was activated to mutagens in the Salmonella/microsome quantitative test system. Liver microsomes from rats pretreated with phenobarbital (PB) increased the mutagenicity of 0.05 mM Tris-BP to 186% of the activity obtained with liver microsomes from untreated rats. The addition of 0.02 mM Tris-BP to V79 Chinese hamster cells co-incubated with liver microsomes from PB-pretreated rats increased the number of mutants by a factor of 9.7. Tris-BP also caused genotoxic and cytotoxic responses in primary monolayers of rat hepatocytes. The relative increase in unscheduled DNA synthesis after treatment with 0.05 mM Tris-BP was 2.3-fold as measured by scintillation counting of radiolabelled thymidine incorporated into DNA of isolated nuclei. The use of hepatocytes isolated from PB-pretreated rats reduced the increases in DNA repair synthesis relatively to that in control cells. Monolayers of hepatocytes from untreated rats co-cultured with Salmonella typhimurium TA100 activated Tris-BP to mutagenic intermediates which were released into the culture medium. The studies with the V79 and liver-cell systems indicate that the reactive intermediates formed from Tris-BP are sufficiently stable and lipophilic to traverse the various membranes from the site of generation to the respective cellular targets. The relative degree of genotoxic responses of bis(2,3-dibromopropyl)phosphate, 2,3-dibromopropylphosphate, tris(2,3-bromopropyl)phosphate, tris(2-bromopropyl)phosphate and 2,3-dibromopropanol in the systems studied did not indicate that these compounds were proximate or ultimate reactive metabolites of Tris-BP in liver-derived activation systems.
在沙门氏菌/微粒体定量测试系统中，磷酸三（2,3 - 二溴丙基）酯（Tris - BP）被激活成为诱变剂。用苯巴比妥（PB）预处理的大鼠肝脏微粒体可使0.05 mM Tris - BP的诱变性增加至未处理大鼠肝脏微粒体所获活性的186%。向与PB预处理大鼠肝脏微粒体共同孵育的V79中国仓鼠细胞中添加0.02 mM Tris - BP，可使突变体数量增加9.7倍。Tris - BP还在大鼠肝细胞原代单层培养物中引起了遗传毒性和细胞毒性反应。通过对掺入分离细胞核DNA中的放射性标记胸苷进行闪烁计数测定，用0.05 mM Tris - BP处理后，非预定DNA合成的相对增加为2.3倍。与对照细胞相比，使用从PB预处理大鼠分离的肝细胞可降低DNA修复合成的增加。未处理大鼠的肝细胞单层与鼠伤寒沙门氏菌TA100共同培养时，可将Tris - BP激活为诱变中间体，并释放到培养基中。对V79和肝细胞系统的研究表明，由Tris - BP形成的反应性中间体足够稳定且具有亲脂性，能够从产生部位穿过各种膜到达各自的细胞靶点。在所研究的系统中，磷酸二（2,3 - 二溴丙基）酯、2,3 - 二溴丙基磷酸酯、磷酸三（2,3 - 溴丙基）酯、磷酸三（2 - 溴丙基）酯和2,3 - 二溴丙醇遗传毒性反应的相对程度并未表明这些化合物是Tris - BP在肝脏衍生激活系统中的直接或最终反应性代谢产物。
