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from SCLC cells and elevated the intracellular cAMP levels (Korman et al., 1986, Cancer Res. 46, 1214). Here 125I-VIP bound specifically and revers- ibly to SCLC cell line NCI-N592. Specific I=sI-VIP binding was inhibited with high affinity by VIP and moderate affinity by secretin. Surprisingly, VIP receptors were not only present on al- most all SCLC cell lines examined by on squamous cell carcinoma, large cell carcinoma and adenocarcinoma cell lines as well. Thus the VIP receptor repre- sents a cell protein present on many tumor cells. Using cell lines NCI-H345 or NCI-N592 ~=sI-VIP was cross linked using disuccinimidylsuberate (DSS) to a 42,000 dalton protein. In contrast, receptors for BN/GRP are larger than are VIP receptors. Previously, we reported that high affinity receptors for BN/gastrin releasing peptide (GRP) were present on SCLC cell line NCI-H345 (Moody et al., 1985, Life Sci. 37, 105). Here within 30 sec after the ad- dition of NB or GRP (i0 nM), the

intracellular Ca ~÷ levels were elevated as determined spectrofluorometrically using Fura-2. In contrast (D-Arg ~, D- Pro =, D-Trp v, Leu~)substance P, which inhibits 12SI-GRP binding to SCLC cells, inhibited the increase in the intracellular Ca ++ levels caused by BN. Thus (D-Arg ~ , D-Pro 2 , D-TrpV, 9 , Leu1~)substance P may function as SCLC BN receptor antagonist and SCLC BN/GRP receptors may utilize Ca ++ as a second messenger. Supported by NCI grants CA- 33767 and CA-42306.

PROOPIOMELANOCORTIN GENE EXPRESSION IN NORMAL AND MALIGNANT TISSUES. Y. Nakai, T. Tsukada, H. Takahashi, T. Usui, J. Fukata, H. Imura. 2nd Division, Depart- ment of Internal Medicine, Kyoto University School of Medicine, Kyoto, 606, Japan.

The mechanism by which tumors elaborate ACTH and other hormones is not yet understood. We studied the biochemical features of extra-pituitary ACTH-producing tumors and possible mechanisms responsible for ectopic production of ACTH. The precursor of ACTH, proopiomelanocortin (POMC), in tumors seems identical to that in the pituitary, although post-translational processing of the precursor is often different in tumors. No gross abnor- malities in genomic DNA and mRNA encod- ing POMC could be detected in tumor tissues. Production of multiple hor- mones is common in ectopic ACTH- producing tumors. These results suggest that tumor cells produce hormones due

to abnormalities in regulation of gene expression. Therefore, we studied the expression of the human POMC precursor gene introduced into pituitary and non- pituitary cell lines. A fragment of human genomic DNA containing the entire POMC gene, together with the neo marker gene, was introduced by transfection into the mouse pituitary tumor cell line atT-20 and the mouse fibroblast L cell line. Transformants were examined for transcripts of the human POMC gene by blot hybridization analysis and S1 nuclease mapping. The results indicated that, in the transformed AtT-20 cells, initiation of human POMC gene transcription and hnRNA splicing were similar to normal human pituitary. Furthermore, the content of the human POMC mRNA in the AtT-20 cells was reduced by addition of dexamethasone to culture medium. In the transformed L cells, however, most of the transcripts of the human POMC gene were not cor- rectly initiated. These observations may suggest that tissue-specific fac- tors are important for the correct transcription of the POMC gene. These tissue-specific factors may be respon- sible for the ectopic ACTH production in neoplasms.

POLYMORPHIC DNA MARKERS REVEAL A LOSS OF CHROMOSOME 3p ALLELES IN THE MAJORITY OF SMALL CELL LUNG CANCER TUMORS. S.L. Naylor (i), A. Marchall (i), B.E. Johnson (2), A. Gazdar (2), J. D. Minna (2), A.Y. Sakaguchi (i). The University of Texas Health Science Center, San Antonio, TX 78284 (i) and NCI-Naval Oncology Branch, Bethesda, Maryland, U.S.A. (2).

Karyotypic studies of small cell lung cancer (SCLC) by Whang-Peng and her associates have identified a dele- tion in chromosome 3 at bands p14-p23. We have undertaken studies to determine if DNA is lost from chromosome 3p in the tumor and to characterize the gene(2) that may be deleted in SCLC. Polymorphic DNA markers were first identified and regionally mapped on chromosome 3. Four probes were specific for the P14-p23 region of chrmosome 3: pMSI-37 detects an MspI polymorphism at teh D3S3 locus at 3p14.2, p12-32 and MspI polymorphism at the D3S2 locus at 3pl.2-p21, and pH3H2 and pH3E4 sub- clones of H3 detect HindIII polymor- phisms at a locus at 3p21. DNA was iso- lated from normal and tumor tissue from 26 individuals with SCLC, ten of which had established tumor cell lines. Two additional individuals had only tumor lines and normal lymphoid lines available. Twenty-seven of the 28