Metabolic Activation of 4-Ipomeanol in Human Lung, Primary Pulmonary Carcinomas, and Established Human Pulmonary Carcinoma Cell Lines

摘要: 4-Ipomeanol (IPO) is a pulmonary-specific toxin that metabolically activated by cytochrome P450 pathway in lung tissue. In this study, IPO metabolism, as determined measurement of [14C]IPO covalent binding, was evaluated diverse sampling 18 established, human cancer cell lines well normal tissue and primary carcinoma obtained at the time thoracotomy from 56 patients with cancer. binding ranged 248 to 1,047 pmol bound per milligram protein 30 minutes (mean +/- SE = 547 62.2). metabolism 12 2,007 covalently 549 60). tissue, values 0 2.566 60, P greater than .3). When were divided into smokers current non-smokers (no tobacco products smoked for 6 mo), no effects cigarette smoking observed either or tumor (P .1 all instances). A wide range metabolic activity among different histological classifications fresh tissues. simultaneously compared individual patients, but positive correlation (r .10; .30). The results clearly demonstrate both cells indicate diversity cancers possess enzyme system(s) necessary bioactivation potentially cytotoxic intermediate. Therefore, continued exploration any possible therapeutic potential appears warranted.