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Relations Between Asbestos Exposure and Lung Cancer SNnRs in Occupational Cohort Studies. Liddell, F.D.K., Hanley, J.A. Department of Epidemiology and Biostatistics, McGill University, Montreal, Canada. Br. J. Ind. Med. 42: 389-396, 1985.

It has long been accepted that exces- sive exposure to asbestos may produce lung cancer but not that there is a con- sistent 'biological gradient'. This can

only be evaluated reliably in studies where, for every individual, exposure has been measured in terms of both dura- tion and intensity. Even now, there are only at most eight such cohort studies of asbestos workers, while formal methods of analysis have been available only recently. These methods, applied in these studies, yield good evidence that the 'exposure-response' relation between ac- cumulated exposure to asbestos and stan- dardised mortality ratios (SMRs) for lung

cancer may be taken as linear, but that at zero exposure the lung cancer SMR is not always unity - not surprising, because of well known difficulties with the choice of reference population and selection problems. This leads to a concept of 'relative slopes' that take account of the background mortality in the cohort and make what appears to be the best use of the available data. Other approaches to the same data, and indeed to all cohort data known, are also considered. Each study is examined as closely as is possible in a short review, and the concepts of line- arity and relative slopes appear justified. The relative slopes (b/a) in the line SMR = a(1 + (b/a).(exposure)) vary much more widely than can be accounted for by dif- ferences in epidemiological methodology; as discussed elsewhere, reasons for the variation seem to lie rather in type and dimensions of asbestos fiber, industrial process, etc. Slopes in the line SMR =

1 + b I (exposure) vary about twice as much ~s do the relative slopes.

Lung Cancer Cell Type and Asbestos Expo- sure. Churg, A. Department of Pathology, Univer- sity of British Columbia, Vancouver, BC V6T IW5, Canada. J. Am. Med. Ass. 253: 2984-2985, 1985.

It is often claimed that adenocarcinoma is the most frequent type of lung cancer seen in workers exposed to asbestos. Careful review of the published data, how- ever, fails to support this claim. Rather, it seems that all types of lung cancers occur in asbestos workers, and the pre- sence or absence of a specific cell type cannot be used to prove or disprove an

association of carcinoma and asbestos exposure.

Lung Cancer Mortality Among Men Living Near an Arsenic-Emitting Smelter. Pershagen, G. National Institute of Environmental Medicine, Karolinska Institute, S-I0401 Stockholm, Sweden. Am. J. Epidemiol. 122: 684-694, 1985.

Etiologic factors for lung cancer were studied by the case-control technique among 636 men, in- cluding 212 with pulmonary carcinoma, who had died between 1961 and 1979 in a county in northern Sweden. Data on smoking habits, occupation, and residence were obtained from a next of kin to each study subject. Validation against data from other sources indicated that the exposure information Was of high quality. A relative risk of 2.0 for lung cancer was seen among men who had lived with- in approximately 20 km from a large copper smelter. The increased risk, which is statistically signi- ficant (p < 0.05), could not be explained by smo- king habits or occupationsl backgrounds. Smelter workers and miners had relative risks for lung cancer of 3.0 and 4.1, respectively. No firm con- clusions can be drawn on the cause of excess lung cancer risk in the smelter area, but it seems plausible that the very substantial emissions to air from the smelter, especially of arsenic, may have played a role.

Underground Mining, Smoking, and Lung Cancer: A Case-Control Study in the Iron Ore ~micipalities in Northern Sweden. Damber, L., Larsson, L.-G. Centre of Oncology, Uni- versity Hospital, University of Umea, S-901 85 Umea, Sweden. J. Natl. Cancer Inst. 74: 1207-1213, 1985.

A case-control study of lung cancer in males was performed in two municipalities in northern Sweden with large iron ore mines. Previous studies had revealed an increased lung cancer risk for underground workers in these mines, with al pro- bability related to radon daughter exposure. Data concerning underground mining and smoking were obtained from questionnaires. All analyses sugge- sted an interaction of a multiplicative type be- tween underground mining and smoking in the causa-

tion of lung cancer in this population. The cal- culated population etiologic fraction was about 45% for underground mining and about 80% for smo- king.

The Role of Radon-222 in the Formation of Bron- chial Carcinoma. Merkel, K. Forschungszentrum Seibersdorf, A-2444 Seibersdorf, Austria. Atemwegs-Lungenkrankh. ii: 109-110, 1985.

In the discussion of the biological effects of ionizing radiation attention paid to radon-222 has

increased during the last decades. The nuclide is formed by the decay of radium-226 which is present in small quantities practically everywhere, so also in building materials. Radon is a gaseous, radio- active natural element. From building materials is diffuses out of the walls of buildings; from outer walls it is blown away by the wind, from

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inner walls it reaches the inside of ad-

jacent rooms. The following dates give rise to the suspicion that as a result of the described modern developments in regions of moderate and cold temperatu- res, 'homemade' radioactivity may consti- tute an important additional source of bronchial carcinoma.

Transforming Potential of a Retrovirus Isolated from Lung Carcinoma of Sheep. Safran, N., Zimber, A., Irving, S.G., Perk, K. The Koret School of Veterinary Medicine, Faculty of Agriculture, Hebrew University of Jerusalem, Rehovot, Israel. Int. J. Cancer 35: 499-504, 1985.

A retrovirus isolated from experimen- tally induced sheep lung carcinoma (SPCTV) was propagated in chronically infected Himalayan tahr ovarian cells and in nor- mal sheep lung cells. Follow-up of infec- tion of the cells with SPCTV showed the appearance of syncytium, plaque formation, partial recovery and the establishment of a chronic infection. Virus-associated reverse transcriptase activity in the medium fluctuated but remained at a con- stantly high level at the stage of chro- nic infection. Stages of type-C virus morphogenesis were demonstrated by elec- tron microscopy. The viral genome was de- tected in both the nucleus and cytoplasm by in situ hybridization. Chronically in- fected cells formed colonies when plated in soft agar. Following subcutaneous in- oculation of chronically infected cells (of fibroblast origin) into nude mice, lymphoid tumors developed at the site of inoculation and in vital organs.

3, BASIC BIOLOGY

Purification from a Human Lung Cancer Cell Line of a Water Soluble Nblecule Mediating Leukocyte Adherence Inhibition for Patients with Lung Cancer. Thomson, D.M.P., Sutherland, M., Durko, M. et al. Montreal General Hospital, Montreal, Que. H3G IA4, Canada. Int. J. Cancer 35: 707-714, 1985.

Soluble lung tumor activity as deter- mined by LAI was enriched by physiocoche- mical methods from chemically-defined spent medium of a lung cancer cell line (NCI-H69). To identify the polypeptide carrying the antigenic determinant, sple- nic lymphocytes of BALB/c mice were immu- nized with the enriched isolate and hy- bridized with mouse plasmacytoma cells. Eight hybrids were cloned successfully and produced MAbs that immunoprecipi- rated principally a single chain of M (r) 40,000 (p40) as well as minor chains of M(r) 25,000 (p25) and M (r) 13,000 (p13)

which were probably degradation products of p40.

On 2D gels, p40 was composed of 7 spots with a pI of 6.3 to 7.6, which was not altered by neuramini- dase digestion. Affinity chromatography with MAb anti-p40 absorbed p40 and LAI activity. The bound and recovered fraction was enriched for p40 and LAI activity. Affinity-purified p40 also contained the previously identified p25 and p13 as well as a M(r) 32,000 peptide (p32). MAb anti-p40 was direc- ted to a common framework determination on p40 since MAb anti-p40 bound to cancer cells from other organs. The comparatively lung cancer organ-speci- fic determinant recognized by leukocytes from lung cancer patients was not recognized by the MAb. Affinity-purified p40 triggered LAI for leukocytes from patients with lung cancer but not for leuko- cytes from control subjects or patients with colon cancer or malignant melanoma in r~gorous blind te- sting. Cross-reactivity was observed with leuko- cytes from patients with breast cancer. LAI activity of affinity-purified p40 seems unlikely to result from an unidentified impurity. Thus a p40 molecule has been purified that is expressed on the membra- nes of lung cancer cells and triggers immunological- ly-mediated LAI.

Genetic Instability of Cell Lines Derived from a Single H~nan Small Cell Carcinoma of the Lung. Engelholm, S.A., Vindel~v, L.L., Spang-Thomsen, M. et al. University Institute of Pathological Anatomy, University of Copenhagen, DK-2100 Copenhagen ~, Denmark. Eur. J. Cancer Clin. Oncol. 21: 815-824,

1985. Specimens from a human small cell carcinoma of

the lung were established as a cell line in vitro. Flow cytometric DNA analysis demonstrated only one tumor cell population in the parent tumor as well as in the early passages in vitro. After six passa- ges in vitro, two new subpopulations with different DNA content appeared. By cloning, permanent cell lines were established from the new subpopulations, whereas the original population stopped growing. The cloned cell lines were characterized by mor- phology, chromosomes analysis, electron microscopy and plating efficiency; the stability of the DNA content was examined regularly by flow cytometric DNA analysis and instability was found in one of the cloned cell lines. Chromosome analysis showed that the cloned cell lines consisted of more than one population after 17 in vitro passages. Both cloned cell lines produced tumors in nude mice. Genetic instability was demonstrated in these mouse- grown tumors as well. Development of resistance to antineoplastic treatment may be due to heterogenei- ty in sensitivity among subpopulations in a tumor. Isolation of populations with different DNA con- tents allows the study of interaction between sub- populations and the observations provide evidence in support of the hypothesis of clonal evolution.

Stability and Utility of the Unique Human Small Cell Carcinoma Line SHP-77. Koros, A.M.C., Klein, E.C., Pan, S. et al. Depart- ment of Infectious Diseases, Graduate School of