MINIMAL EFFECTS OF ACRYLONITRILE ON PULMONARY AND HEPATIC CELL INJURYENZYMES IN RATS WITH INDUCED CYTOCHROME-P450

Acrylonitrile (AN) has many industrial applications but is a known car cinogen in animals and a suspect human carcinogen. Its toxicity is gen erally associated with its bioactivation, the initial step of which is epoxidation by cytochrome P450. While the hepatotoxicity and pneumoto xicity of AN in naive rats is generally low, the purpose of this study was to investigate the pneumotoxicity and hepatotoxicity of AN in adu lt male Sprague-Dawley rats and evaluate interactions with agents that may alter its metabolism. Five agents, phenobarbital, beta -naphthofl avone, pyridine, ethanol, and acetone, were administered prior to AN a s inducers of CYP2B, CYP1A, and CYP2EI. Pneumotoxicity was measured as increases in gamma-glutamyltranspeptidase (GGT) and lactate dehydroge nase (LDH) in bronchoalveolar lavage fluid (BALF). Hepatotoxicity was measured as increases in serum sorbitol dehydrogenase (SDH). AN (I mmo l/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 G GT, but had little effect on SDH or LDH. Acetone plus AN caused an inc rease in mortality and some indication of pneumotoxicity, but lung and liver were histologically normal. Thus AN alone even at a high dose h ad no effect on the liver or lung and minimal effects following induct ion of cytochrome P450 by acetone.