In vitro metabolism of N-nitrosopyrrolidine by rat lung subcellular fractions: alpha-hydroxylation in a non-target tissue.

N-Nitrosopyrrolidine is carcinogenic for the liver but not for the lung. Optimal conditions for the metabolism of N-nitrosopyrrolidine (NO-PYR) by rat lung microsomes and post-microsomal supernatant were determined. Neither lung nor liver subcellular fractions were able to form detectable amounts of 3-hydroxyNO-PYR. Liver and lung microsomes could only alpha-hydroxylate NO-PYR, and even though the rates of lung reactions were considerably slower than those of liver, similar products were produced by the action of both lung and liver supernatants on microsomal products. The apparent Km for the lung microsome plus supernatant reaction was approx. 20 mM as compared with 0.36 mM for the liver system. Since both the target and non-target tissue extracts could metabolize NO-PYR by the same pathways, we speculate that alpha-hydroxylation of NO-PYR may be a necessary, but not sufficient cause for its carcinogenic actions.