PEPTIDE AMIDATING ACTIVITY IN HUMAN BRONCHOALVEOLAR LAVAGE FLUID

Monitoring respiratory epithelial biology may reveal individuals with incipient lung cancer. The expression of neuroendocrine (NE) markers i n pulmonary epithelium is thought to be central to lung development, r epair of injury and may contribute to carcinogenesis, In this study, w e evaluate several candidate NE markers to determine the feasibility o f prospective analysis of clinical specimens. The potential NE markers include the enzyme L-DOPA decarboxylase (DDC), the neuropeptide gastr in releasing peptide (GRP), and peptidyl-glycine alpha-amidating monoo xygenase (PAM), the bifunctional enzyme responsible for the final bioa ctivation step of many neuropeptides. A comparison of PAM activity and DDC levels in 30 lung cancer cell lines indicated that peptide amidat ing activity may be an indicator of NE status. Bronchoalveolar lavage (BAL) fluid from subjects al risk of developing second primary lung ca ncer and from volunteers was obtained. The activity of the first PAM e nzyme, peptidylglycine alpha-hydroxylating monooxygenase (PHM), ranged from not delectable to 507 pmol/h/mg protein in 57 specimens. The sec ond PAM enzyme, peptidylamidoglycolate lyase (PAL), ranged from not de tectable to 414 pmol/h/mg protein in 56 specimens. Using cluster analy sis by the average linkage method, a group of enzyme values with PHM g reater than 230 pmol/h/mg protein was determined. Long-term follow-up of these patients for new second primary lung cancers may help to dete rmine the potential predictive value of PAM detected in the BAL fluid.