Fort D J, Rogers R L, Stover E L, Finch R A
Fort Environmental Laboratories, Inc., Stillwater, OK, USA.
Drug Chem Toxicol. 2001 May;24(2):103-15. doi: 10.1081/dct-100102604.
The developmental toxicity of cyclophosphamide, coumarin, 2-acetyl-aminofluorine (2-AAF), and trichloroethylene (TCE) was assessed with Frog Embryo Teratogenesis Assay: Xenopus (FETAX). Late Xenopus laevis blastulae were exposed to each test material for 96-h in two separate static-renewal tests with and without the presence of five differently induced exogenous metabolic activation systems (MAS). The MAS consisted of Aroclor 1254- (Aroclor 1254 MAS), isoniazid- (INH MAS), phenobarbital- (PB MAS), or beta-naphthoflavone- (beta-NF MAS), or a post-isolation mixture (mixed MAS) of INH-, PB-, and beta-NF-induced rat liver microsomes. Addition of the Aroclor 1254 MAS bioactivated cyclophosphamide, coumarin, 2-AAF, but not TCE. Addition of the PB MAS bioactivated cyclophosphamide, weakly bioactivated coumarin and 2-AAF, but had no effect on TCE developmental toxicity. The beta-NF MAS bioactivated coumarin and 2-AAF, weakly bioactivated cyclophosphamide, but did not alter the developmental toxicity of TCE. Addition of the INH-induced MAS only bioactivated TCE, whereas the post-isolation mixed MAS bioactivated each test material. Based on LC50 and EC50 (malformation) values, embryo growth, and types and severity of induced malformations, each test material was developmentally toxic. Use of post-microsome isolation mixtures from differentially induced rat livers increased the efficacy of the exogenous MAS routinely used by FETAX.
采用非洲爪蟾胚胎致畸试验（FETAX）评估了环磷酰胺、香豆素、2-乙酰氨基芴（2-AAF）和三氯乙烯（TCE）的发育毒性。在两个单独的静态更新试验中，将晚期非洲爪蟾囊胚暴露于每种测试物质96小时，试验分别在有和没有五种不同诱导的外源性代谢活化系统（MAS）存在的情况下进行。MAS由多氯联苯混合物Aroclor 1254（Aroclor 1254 MAS）、异烟肼（INH MAS）、苯巴比妥（PB MAS）或β-萘黄酮（β-NF MAS），或由INH、PB和β-NF诱导的大鼠肝微粒体的分离后混合物（混合MAS）组成。添加Aroclor 1254 MAS可使环磷酰胺、香豆素、2-AAF生物活化，但不能使TCE生物活化。添加PB MAS可使环磷酰胺生物活化，使香豆素和2-AAF弱生物活化，但对TCE的发育毒性没有影响。β-NF MAS可使香豆素和2-AAF生物活化，使环磷酰胺弱生物活化，但不改变TCE的发育毒性。添加INH诱导的MAS仅使TCE生物活化，而分离后混合MAS使每种测试物质生物活化。根据半数致死浓度（LC50）和半数致畸浓度（EC50）值、胚胎生长情况以及诱导畸形类型和严重程度，每种测试物质都具有发育毒性。使用来自不同诱导大鼠肝脏的微粒体分离后混合物提高了FETAX常规使用的外源性MAS的功效。
