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Center, Duarte, California 91010, U.S.A. Progress against lung cancer requires

clinical/basic-science focus upon pre- neoplasia and early cancers, impossible to achieve with studies limited to humans. Therefore, a canine squamous cell lung cancer model has been developed. We have studied 104 dogs exposed by 9 regimens to the focal endobronchial chemical car- cinogens benzopyrene (BP), nitrosome- thylurea (NMU), methylcholanthrene (MCA), and dimethylbenzanthracene. The first cancer was induced by BP and NMU in 1/7 (14%) dogs after 5-~ years, but the most recent regimen (30mg MCA q 2-3 wks) produced 8/10 (80%) cancers within 2 years of first exposure; 2 recent can- cers are being serially passaged in athy- mic nude mice, now at the fourth trans- plant generation, and the model has been successfully used in 15 dogs in pre- clinical trials to show the safety and efficacy of a new high pressure bronchial washing system for sampling the bronchi- al epithelium. The predictable, repro- ducible, eventually metastasizing neo- plastic continuum begins with columnar and basal hyperplasia and squamous meta- plasia; it evolves into squamous meta- plasia with atypia in 6-18 weeks. The interval (about 20 months) until invasive cancer develops provides unique opportu- nity to sample repetitively from the preneoplastic bronchial mucosa. Serial cytologic specimens studied by image ana- lysis have revealed progressive increase in mean DNA content from normal (diploid) to atypical squamous metaplasia to cancer (>tetraploid) with significant (p<0.01) differences between diagnostic catego- ries.

We now have a large animal model of squamous cell carcinoma amenable to sur- gical methods; the reproducible preneo- plastic events occur in a time span short enough to be fiscally defensible, and long enough to permit biologic dissection during the development of bronchogenic cancers at predictable, preselected sites.

Growth In Nude Mice and Resistance Pre- dictive Tests of Non Small Cell hmg Carcinoma (NSCLC) Related to Prognosis. Drings, P., Mattern, J., Sonka, J., Vogt- Moykopf, I., Wayss, K., Volm, M. Chest Hospital Rohrbach, German Cancer Research Center, Heidelberg, FRG.

The purpose of the study was to assess the clinical prognostic significance of growth of NSCLC into nude mice as well as of a short term predicting resistance.

One hundred seventy one primary untreat- ed NSCLC were heterotransplanted into nude mice with an overall success rate of 46%.

Fifty cases (=29%) could be maintained

by serial transplantation. Lung tumors were divided into two groups depending on whether they have shown growth or not and correlated with the survi- val time of the corresponding patients. A relation- ship does not exist between growth of the tumors in nude mice or establishment of cell lines and prognosis of patients.

Furthermore, a total of 178 lung carcinomas we- re investigated by means of a short term test for predicting resistance. The basic feature of this short term test for predicting resistance is mea- surement of changes in incorporation of radioac- tive nucleic acid precursors after addition of cy- tostatic agents by scintillation counting. Patients with in vitro resistant tumors died earlier than those with sensitive tumors.

In conclusion, short term test for predicting resistance represent a useful tool in addition to current tumor parameters of estimating prognosis of patients with NSCLC whereas growth of SCLC into nude mice has not prognostic significance.

Biological Characterization of Transformed Rat Tracheal Epithelial (RTE) Cell Colonies in Cultu- re. Fitzgeral, D.J., Kitamura, H., Barrett, J.C., Nettesheim, P. Natl. Inst. Env. Hlth. Sci., Res. Triangle Pk., NC 27709, U.S.A.

In an accompanying abstract (Kitamura et al.,) the morphologic features of nontransformed (Types I-II) and transformed (types III-IV) RTE cell co- lonies which emerge 3-5 wks after MNNG treatment of primary RTE cell cultures, are described. In this study, we examined some biological characte- ristics of these different types of RTE cell colo- nies.

Five weeks after exposure of RTE cell cultures to MNNG, colonies were identified under phase mi- croscopy. Some colonies were incubated for 24 hrs with H-thymidine and were processed for autoradio- graphy to determine labelling indices, which were as follows (% labeled cells); type I 7 ~ 6, type II 21 + 13, type IIl 28 + 8, type IV 27 ~ 9. To determi--ne the fate of th~ different types of colo- nies, colonies were classified at 5 wks and main- tained for an additional 4 wks. Of the type I colonies, 20/27 senesced, 6/27 failed to grow, and 1/27 progressed to type III. Of the type II colo- nies, 3/22 regressed, 7/22 failed to grow, while 12/22 progressed to become types III-IV. Cells from different colony types were replated to assess the proportions of colony fo~nning units (CFU) and transformed CFU (i.e., CFU able to form trans- formed colonies). The data indicate that such pro- portions are similar for type II-III colonies but are considerably larger in type IV colonies.

These results support the notion based on mor- phologic studies that type I colonies are relative- ly inactive. Type II colonies, however, which so far have also been judged to be nontransformed, require reappraisal since they have labelling in- dex and CFU fraction similar to type III colonies; furthermore, in 50% of the cases, they progress to type III-IV colonies.