Vila M C, San Martín deViale L C
Toxicology. 1982;25(4):323-32. doi: 10.1016/0300-483x(82)90110-x.
In the present study we investigated the porphyrinogenic ability of 4 pesticides: chlordane, endosulfan, parathion and malathion, all of which are widely used in agriculture. In order to determine whether they affect the heme biosynthetic pathway we studied, in 17-day old chick embryo liver "in ovo", their effects on the amount of porphyrins and on the activity of delta-ALA synthetase (ALA-S), the first and rate limiting enzyme of this pathway. All of them induced hepatic porphyrin accumulation to a different extent compared with dimethylsulfoxide (DMSO) controls. Parathion as well as endosulfan promoted remarkable increases, chlordane raised porphyrin level in a lower degree and malathion slightly modified it. However, the accumulation observed with malathion was markedly enhanced if the period of incubation was extended to 48 h and, even more, if a second dose was injected during these 48 h. When ALA-S activity was analyzed in the chick embryos treated with parathion or endosulfan no alteration could be found in spite of producing noticeable accumulation of porphyrins. In contrast, chlordane promoted a statistically significant elevation of ALA-S as well as malathion which produced the highest induction observed. These results show that not only organochlorinated but also organophosphorous pesticides affect heme metabolism and that induction of ALA-S and porphyrin accumulation are not parallel.
在本研究中,我们调查了4种农药(氯丹、硫丹、对硫磷和马拉硫磷)的致卟啉生成能力,所有这些农药都在农业中广泛使用。为了确定它们是否影响我们所研究的血红素生物合成途径,我们在17日龄鸡胚肝脏中“在卵内”研究了它们对卟啉量以及对δ-氨基-γ-酮戊酸合成酶(ALA-S)活性的影响,ALA-S是该途径的第一个也是限速酶。与二甲基亚砜(DMSO)对照相比,它们都不同程度地诱导了肝脏卟啉积累。对硫磷以及硫丹促使卟啉显著增加,氯丹使卟啉水平升高程度较低,而马拉硫磷使其略有改变。然而,如果孵育期延长至48小时,尤其是在这48小时内注射第二剂时,马拉硫磷观察到的积累会显著增强。在用对硫磷或硫丹处理的鸡胚中分析ALA-S活性时,尽管产生了明显的卟啉积累,但未发现有变化。相比之下,氯丹促使ALA-S有统计学意义的升高,马拉硫磷也有升高,且产生了观察到的最高诱导作用。这些结果表明,不仅有机氯农药而且有机磷农药都会影响血红素代谢,并且ALA-S的诱导和卟啉积累并不平行。