卡铂的致突变与致畸胎研究

MUTAGENIC AND TERATOGENIC STUDIES OFCARBOPLATIN

本文用Ａｍｅｓ试验、小鼠骨髓微核试验及人外周血淋巴细胞染色体畸变试验研究了卡铂的致灾变作用，同时用受孕大鼠研究了卡铂的致畸胎作用。结果表明，该药只有显著的致空变及胚胎毒作用。在Ａｍｅｓ试验中，卡铂浓皮１０，１００，５００，１０００和５０００μｇ／对ＴＡ１０２菌株均有显著的回复突变作用，在微核试验中，卡铂２０，４０，６０ｍｇ／Ｋｇ剂量组均诱发微核率显著增高，大剂量组高达８６％。在染色体畸变试验中，卡铂引起染色体畸变率５．０μｇ／ｍｌ组为１２．０％（－Ｓ９）；１０．０％（＋Ｓ９）；５０．０ｇ／ｍｌ组为２１．０％（－Ｓ９），１８．０％（＋Ｓ９）。与对照组比较有显著差异。大鼠致畸胎试验表明，卡铂２０ｍｇ／ｋｇ间隔２日给药２次，具有明显的胚胎毒作用，死胎率达４１．７％，多肋率为２２，６％，但未见外观及内脏器官畸形。

Mutagenicity and teratogenicity of carboplatin have been reported in this paper.Its mutagenesis has been observed in the following detection, Ames test showd thatrevertants of TA102 strain increase apparently at concentration 10, 100 , 500,1000,5000μg/plate. Micronuclei test of mouse bone marrow demonstrated that the drug can induceremarkable increase of micronuclei frequencies at doses 20, 40, 60 mg/Kg. Chromosomalaberration test indicated that the chemical can apparently damage chromosome of humanperipheral blood lymphocytes at concentration 5.0,50.0μ g/ml.In teratogenic test on ratsembrotoxicity has been found at the dose of 20 mg/Kg, but malformation of internalorgans and appearance of fetuses not.