120 Abstracts/Lung Cancer I2 (1995) 113-160 Spontaneous production of ioterleukin-8 by human lung cancer cells and ita augmentation by tumor oecmsis factor alpha and interkukin- 1 d protein and mRNA levels Mizuno K, Sone S, Orino E, Mukaida N, Matsushima K, Ogura T. Third Department Internal Medicine, University of Tokushima, School ofMedicine, Kuramoto-cho 3. Tokushima 770. Oncology (Switzerland) 1994;51:467-71. A cell-tocell interaction between tumors and host inflammatory cells is important for the subsequent cancer progression or regression. We examined the expression of interleukin-8 (IL-S) mRNAs by 9 human lung cancer cell lines and the influences of cytokines on IL-8 production and its gene expression. Substantial expressions of IL-8 gene were detected in 3 lung cancer cell lines (SERF-LC-OK, Lu-134-A-H, YO- 88 cells). Moreover, 4 lung cancer cell lines (RBRF-LC-MS, RERF- LC-OK, A549 and YO-88) were used to examine the effects ofexogenous cytokines - interlcukin-16 (IL-l@, tumor necrosis factor a (TNFa) and granulocyte-macrophage colony-stimulating factor-on IL-8 production by the cells at protein. and gene levels. TNFa and IL-18 significantly augmented the levels of mRNA expression for IL-8 and its production. These observations indicate that tumor-derived IL-8 may be important in recruiting inflammatory neutrophils and promoting interaction between lung cancer and inflammatory cells. Analysis of cytocbrome P450 2El genetic polymorphisms in relation to human lung cancer Kato S, Shields PG, Caporaso NE, Sugimura H, Trivers GE, Tucker MA et al. Laboratoty of Human Carcinogenesis, Division of Etiology, National Cancer Institute, Bethesda, MD 20892. Cancer Epidemiol Biomarkers Prev 1994;3:515-8. Human cancer risk assessment using molecular genetic techniques is a rapidly emerging field. Many studies suggest that both inherited and acquired genetic predispositions play an important role in carcinogenesis. Cytochrome P450 (CYP) 2El is involved in the metabolic activation of N-nitrosamines and other low molecular weight compounds. A recently described genetic polymorphism of CYP2El PraI restriction fragment length polymorphism (RFLP)] has been associated with an increased risk of lung cancer in Japanese. We have assessed the allelic frequency of three RFLPs (PstI, RsaI, and DraI) in African-Americans (n = 109). Caucasian Americans (n = l53), and octogenarian Japanese (n = 42). and also in a United States case-control study of lung cancer (histologically confirmed lung cancer, n = 58; controls, n = 56; total, n = 114). The relationship of the CYP2El DraI polymorphism to other CYPZEI polymorphisms (PstI and RsaI RFLP) was examined. The allelic frequency of the DraI C minor allele for all subjects was 0.09 in Caucasians, 0.09 in African-Americans, and 0.31 in Japanese.. In the caseantrol study of lung cancer, no association of the CYP2El DraI genotype with lung cancer was found (odds ratio, 1.57,95% confidence interval, 0.59-4.18). Comparison after discordant CYP2El genotypes suggests the presence of different haplotypes in Americans and Japanese. These results indicate that the CYP2El DraI RFLP is probably not a cancer risk factor in United States Caucasian or African- Americans, although statistical power is limited given the low frequency of the CYP2El DraI C minor alleles. A homozygoua deletion in a small cell lung cancer cell line involving a 3~21 region with a marked instability io yeast artificial chromosomes Kok K, Van den Berg A, Veldhuis PMJF, Van der Veen AY, Franke M, Schoenmakers EFPM et al. Department ofMedical Genetics, University of Groningen, A. Deusinglaan 4, 9713 AW Gmningen. Cancer Res 1994;54:4183-7. All types of lung carcinoma are characterized by a high frequency of loss of sequences from the short arm of chromosome 3, the smallest regionofoverlapcontainingD3FlSSZ in bandp21. Herewecharacterize a 44O-kilobase segment from this region, which we found homozygously deleted in one of our small cell lung cancer-derived cell lines. The homozygous deletion maps between UBElL and ZnF16, just centromeric to D3F15S2. Yeast artificial chromosomes with inserts originating from the deleted region are very unstable and readily lose parts of their insert. 5-ET(lD) receptor type is involved in stimulation of cell ptuliferation by serotoaio in human small cell lung carcinoma Cattaneo MG, Palazzi E, Bondiolotti G, Wncenti LM. Department of Pharmacology, School OfMedicine. Universiy ofMilan, fia Vanvitelli 32,20129 Milan. Eur J Pbarma~~l Mol Pharmacol Sect 1994;268:425- 30 Serotonin (5-hydroxytryptamine, 5-HT), a neurotransmitter and vasoactive agent, is contained in two small cell lung carcinoma cell lines GLCS and NCI-N-592 and is released in the culture medium. It also stimulates DNA synthesis in the same cell lines. In GLCS cells tbis mitogenic effect is not counteracted by ketanserin, ICS 205-930 and GR 113-808 which are antagonists of the 5-HT,, 5-HT, and 5-HT, receptors, respectively. On the contrary, the antagonists metergoline, methysergide, SD2 21-009 and methiothepin inhibit the 5-HT- stimulated incorporation of [‘wthymidine in GLCS cells. The S-HT., agonist sumatriptan is capable of mimicking 5-I-IT action on cell proliferation. Both sumatriptan and S-HT inhibit adenylate cyclase activity at doses which correlate with the mitogenic effect. We conclude that a 5-HT(lD) receptor type contributes to the mitogenic effect of 5- I-IT in GLCS cells. This is the first demonstration of an involvement of the 5-HT,, receptor type in human cell proliferation. The design of specific antagonists for this type of receptor might be useful for the growth control of this very aggressive tumor. Analysis of urinary fibmnectin (UPN) using buman luagcancerceils transplanted into nude mice Nonaka M, Kadokura M, Tanio N, Yamamoto S, Takaba T. Department of Sutgety, Showa University School ofMedicine, Tokyo. Lung Cancer (Japan) 1994:34:363-9. Fibronectin is widely distributed in the body, i.e. in plasma, on basement membrane and so on. Since great amounts of urinary fibronectin (UFN) are seen in patients with cancer, UFN is considered to be related with cancer growth and metastasis. In this study, we transplanted human lung cancer cells (PC-9, PC-14) into athymic nude mice subcutaneously, and measured both the concentration of UFN and tumor size of the mice periodically. We also analyzed the changes of UFN in relation to the growth of the tumor. As a result, the levels of UFN increased after cancer cell transplantation, and a correlation between tumor growth and UFN levels was observed statistically. Histopathologically, these subcutaneous tumors consisted of cancer cells, and they were positive for immunohistochemical staining with the ABC method using anti- fibronectin monoclonal antibody. No metastatic lesions were se-en in the mice. We conclude that urinary fibronectin is derived from cancer cells and increases with the growth of the tumor. Establishment of a new lung sarcoma cell line from a human lung carcinosarcoma Leibovitz A, Wymer J, Massey K, Thompson FH, Nelson MA. Department of Pathology, College ofMedicine. University ofArizona, AZ. Cancer Lett 1994;82:145.52. A cell-line (UACC 2561). was established from a biopsy specimen of a lung carcinosarcoma. The patient bad Stage 111 non-small cell lung