Hood R D, Kuczuk M H, Szczech G M
Teratology. 1978 Feb;17(1):25-9. doi: 10.1002/tera.1420170108.
Aspergillus ochraceus and Fusarium tricinctum are food contaminating molds whose toxic metabolites, ochratoxin A and T-2 toxin, are known mammalian teratogens. In order to determine the possible effects of simultaneous exposure to such environmental agents, ochratoxin A (2 or 4 mg/kg) and T-2 toxin (0.5 mg/kg) were injected ip, either together or individually, in CD-1 mice on gestation days 8 or 10. Ochratoxin induced craniofacial malformations when given alone on day 8, but not on day 10. T-2 toxin induced tail and limb anomalies particularly when given on day 10. When the two toxins were given together on day 10, ochratoxin exacerbated the incidence of T-2 induced gross malformations. An increase in fetocidal effects was also noted in groups treated at the high dose combination on either day, and effects on fetal growth of the high dose combination given on day 10 were greater than those of the other treatments. Few skeletal or visceral malformations were noted. These results indicated that two teratogens with presumably differing mechanisms of teratogenesis may have additive effects when administered concurrently to the same animal. Such results could be due to generalized toxic effects on the fetus or to more specific mechanisms, but further information is needed to differentiate between the two possibilities.
赭曲霉和三线镰刀菌是污染食物的霉菌,其有毒代谢产物赭曲霉毒素A和T-2毒素是已知的哺乳动物致畸剂。为了确定同时接触这些环境因子可能产生的影响,在妊娠第8天或第10天,将赭曲霉毒素A(2或4mg/kg)和T-2毒素(0.5mg/kg)单独或一起腹腔注射到CD-1小鼠体内。单独在第8天给予赭曲霉毒素时可诱导颅面畸形,但在第10天则不会。T-2毒素尤其在第10天给予时会诱导尾部和肢体异常。当两种毒素在第10天一起给予时,赭曲霉毒素会加剧T-2诱导的严重畸形的发生率。在任何一天接受高剂量组合治疗的组中还观察到杀胚胎作用增加,并且在第10天给予高剂量组合对胎儿生长的影响大于其他治疗组。未观察到明显的骨骼或内脏畸形。这些结果表明,两种致畸机制可能不同的致畸剂同时给予同一动物时可能具有相加作用。这种结果可能是由于对胎儿的普遍毒性作用或更具体的机制,但需要更多信息来区分这两种可能性。