34

Bombesin- An Autocrine Growth Factor for H~an Small Cell Carcinoma Cell Lines? Bergh, J., Brodin, O., Nilsson, S. Depart- ment of Oncology and Pathology, Universi- ty of Uppsala, Sjukhusv~gen i0, S-751 85 Uppsala, Sweden.

Human small cell carcinoma (SCC) cell lines are characterized by expression in high quantities of a spectrum of neuro- endocrine markers: Neurofilaments, neu- ron-specific enolase, neurosecretory gra- nules, bombesin and calcitonin. These mar- kers are missing or expressed in conside- rably lower levels in lung cancer cell lines of non-SCC origins. Bombesin has been, described to be produced by SCC cell li- nes and bombesin has also been proposed to be a specific autocrine growth factor for SCC in experiments using bombesin antibodies, hence resulting in decreased proliferation.

We have thus examined SCC cell lines with variable bombesin production and proliferation rates. Bombesin was added (Supernatants from cell lines with "high"

bombesin production and purified bombe- sin) to SCC cell lines, with low endo- genous production of bombesin to the su- pernatants.

Addition of purified bombesin and bombesin containing supernatants seemed to enhance the proliferation in cell lines having low endogenous production. Most interestingly, the cell lines with low production had quite a rapid proli- feration rate even without addition of bombesin, thus indicating also other me- chanisms to be involved in growth re- gulation of SCC.

Development of A Model for H~an Bron- chial Carcinoma in the Rat. Kal, H.B., van Bekkum, D.W. Radiobiolo- gical Institute TNO, Rijswijk, The Ne- therlands.

Experimental lung tumour models are needed to deepen the insight into the biological behaviour of human bronchi- al cancer and ideally, to predict re- sponses in the human situation.

To develop a model for human bronchi- al cancer lung tumours were induced by ionizing radiation emitted from Ir-192 or 1-125 isotopes implanted in the lung of WAG/Rij rats. These tumours, five different squamous cell carcinomas were serially transplanted subcutaneously in syngeneic recipients.

The histopathological characteristics of the tumours upon successive passages, which extended over one to three years, remained the same. Tumour volume doubling times ranged initially from three to eight days; two to three years later these were three to eight days. The sen-

sitivity of the tumours growing subcutaneously

for x-radiation, methotrexate, vinblastine, cis- platinum, adriamycin and mitomycin C was determi- ned in terms of growth delay induced by the treat- ment. The results suggest that some of these rat tumours show a similar pattern of drug resistance as is described for human squamous cell carcinoma of the lung.

A method has been developed to implant tumour fragments in a specific lobe of the lung by a sur-

gical procedure. It is a modification of a method described by Stanton et al., J.N.C.I., 49, 867,

1972. With roentgenograms the growth of the tumour can be monitored. The sensitivity to various treat- ment modalities of tumours growing in the lung is being compared with that of the same tumours grow- ing subcutaneously. By this approach it is attempt- ed to develop a realistic experimental model for human lung cancer in rats.

Comparative Study of Oncogene and Hormone Gene Expression in Small Cell Carcinoma of the Lung (SCCL). Sorenson, G.D., Cate, C.C., Pettengill, O.S. Dart- mouth Medical School, Hanover, NH, U.S.A.

Cytogenetic studies of SCCL indicate that many of the tk~nors have multiple chromosomal abnorma- lities, some of which in other cell systems have been correlated with gene duplication. A series of SCCL cell cultures has been screened for am- plification and expression of multiple genes in- cluding the oncogenes myc and myb and the hormo- ne genes calcitonin-calcitonin gene related pep- tide (CT-CGRP), growth hormone (GH) and pro-opio- lipomelanocortin (POMC). DNA was isolated, EcoRl digested and evaluated by hybridization and Sou- thern blot analyses. Two cell lines (DMS 55 and 273) out of sixteen had markedly amplified c-myc genes with 12.5 Kb bands comparable in intensity to the positive control, HL60 promylocytic c~ll line. Mos~ OC the cell line~.hadlamplified c-myb compa- red to cultured human fibroblasts. CT-CGRP and GH genes were not amplified although the POMC gene appeared to be amplified in some cell lines in- cluding a high secretor of ACTH (DMS 79). As a means ~f evaluating the expression of these genes, poly A RNA was isolated and evaluated by Northern blot analyses. Expression of c-myc was variable but significant expression was observed in mul- tiple cell lines including those without evidence of marked gene amplification. The expression of the CT-CGRP gene was variable among cell lines. In DMS 53 it was expressed largely as CT mRNA and in DMS 153 it was expressed mainly as CGRP mRNA. This indicates that these two cell lines process the primary transcript of this gene differently and produce mainly one or the other mRNAs. These studies illustrate the variable expression of multiple genes in SCCL and indicate that high CT Or CGRP production is not associated with CT-CGRP gene amplification.

Transfection of the C-Myc Proto-Oncogene into Classic Small Cell Lung Cancer (SCLC) Cell Lines Causes Phenotypic Changes Associated with C-MYC