Felten R K, DeNicola D B, Carlson G P
School of Health Sciences, Purdue University, West Lafayette, IN 47906, USA.
Drug Chem Toxicol. 1998 May;21(2):181-94. doi: 10.3109/01480549809011646.
Acrylonitrile (AN) has many industrial applications but is a known carcinogen in animals and a suspect human carcinogen. Its toxicity is generally associated with its bioactivation, the initial step of which is epoxidation by cytochrome P450. While the hepatotoxicity and pneumotoxicity of AN in naive rats is generally low, the purpose of this study was to investigate the pneumotoxicity and hepatotoxicity of AN in adult male Sprague-Dawley rats and evaluate interactions with agents that may alter its metabolism. Five agents, phenobarbital, beta-naphthoflavone, pyridine, ethanol, and acetone, were administered prior to AN as inducers of CYP2B, CYP1A, and CYP2E1. Pneumotoxicity was measured as increases in y-glutamyltranspeptidase (GGT) and lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF). Hepatotoxicity was measured as increases in serum sorbitol dehydrogenase (SDH). AN (1 mmol/kg ip) had little effect on liver or lung, even when given following most of the inducing agents. AN (1.5 mmol/kg) caused an increase in GGT, but had little effect on SDH or LDH. Acetone plus AN caused an increase in mortality and some indication of pneumotoxicity, but lung and liver were histologically normal. Thus AN alone even at a high dose had no effect on the liver or lung and minimal effects following induction of cytochrome P450 by acetone.
丙烯腈（AN）有许多工业用途，但它在动物中是已知的致癌物，在人类中是疑似致癌物。其毒性通常与其生物活化作用有关，生物活化的第一步是由细胞色素P450进行环氧化。虽然在未接触过AN的大鼠中，AN的肝毒性和肺毒性通常较低，但本研究的目的是调查AN对成年雄性Sprague-Dawley大鼠的肺毒性和肝毒性，并评估其与可能改变其代谢的药物之间的相互作用。在给予AN之前，给予五种药物，即苯巴比妥、β-萘黄酮、吡啶、乙醇和丙酮，作为CYP2B、CYP1A和CYP2E1的诱导剂。肺毒性通过支气管肺泡灌洗液（BALF）中γ-谷氨酰转肽酶（GGT）和乳酸脱氢酶（LDH）的增加来衡量。肝毒性通过血清山梨醇脱氢酶（SDH）的增加来衡量。AN（1 mmol/kg，腹腔注射）对肝脏或肺部几乎没有影响，即使在大多数诱导剂给药后给予也是如此。AN（1.5 mmol/kg）导致GGT增加，但对SDH或LDH几乎没有影响。丙酮加AN导致死亡率增加，并出现一些肺毒性迹象，但肺和肝脏在组织学上正常。因此，单独使用AN即使高剂量也对肝脏或肺部没有影响，在丙酮诱导细胞色素P450后影响也很小。
