Lung cancer in women

120 accumulated that supports involvement of proteolytic enzymes and oxidants in the pathogenesis of smoking-induced lung injury. Still at issue are the host factors that modulate the effects of smoking in the individual subject It remains unclear why a large proportion of smokers are protected fmm the deleterious effect of tobacco exposure. A potential problem with the pmtease-antipmtease hypothesis is that its focus may be too narrow. Whereas it appears that the balance between proteolytic enzymes and their inhibitors is important in determining the integrity of pulmonary structure and function, the role of other intlammatory pathways in the pathogenesis of smoking-induced lung injury remains to be elucidated. Furthermore, lung injury contingent on the effects of pmteolytic enzymes or oxidants may be signiticandy influenced by either genetic or environmental factors. As recently reviewed, clarification of important protective mechanisms that modulate the effects of cigarette smoking may await the application of biochemical and molecular methodology to traditional epidemiologic analyses of smoking-relateddisease. Current informationderived from clinical and experimental studies provides a reasonable explanation for the apparent link between smoking and chronic obstructive pulmonary disease. However, elucidation of the truly important effecters of lung injury present incigarette smokeand thedefensesagainsttheseagentsremains the major challenge for future investigation.

Lung

cancer

in women

Loewen GM, Roman0 CF. Respiramy Pulmonary Division, Deparmenr

Care and Sraff Physician, House of rhe

of Inrernal Medicine.

GoodSammkn, Watertown,NY 13601. J Fsyctit Dtugs 198%21:31921. In 1983, lung cancer exceeded breast cancer as the leading cause of death in American women. Between 1950 and 1985 there was a 500% increase in lung cancer deaths in women, and this trend is not expected to improve in the next decade. There is no corresponding increase in the overall incidence of lung cancer in the general population of the United States. Cigarette smoking is clearly the primary risk factor in this group and the role of passive smoking remains controversial. Various other etiologic factors, including a shift in occupational exposure, may play a minor role in the development of lung cancer in women. The risk of lung cancer in smokers does not return to that of nonsmokers until 15 years after smoking cessation. If the incidence of smoking in American women was reduced to pm-1950 levels, it is estimated that lung cancer in women would once again become a rare finding after the year 2000. Changes in patterns of cigarette smoking and lung cancer risk: Results of a case-control study Benhamou E, Benhamou S, Auquier A, Flamant R. Deparremenl de Starisdque Medicale, Ins&w Gustave Roussy. 94805 Villeju$ Br J Cancer 1989;60:601-4. Data from a case-control study on lung cancer were used to evaluate how changes in ciganztte habits, mainly smoking cessation, switch from non-tiltertofilterbrands,fmmdarktolighttobacco,orfrom handrolled to manufactured cigarettes, and reduction in daily consumption influence lung cancer risk. The results presented concern all males, exclusive cigarette smokers. involved in the study, i.e. 1,057 histologically confirmed lung cancer and 1,503 matched controls. The general decrease in lung cancer risk with the years since cessation was also found in each subgroup of cigarette exposure defined by duration of smoking, daily consumption and type of cigarettes smoked. Among smokers who had given up smoking from less than 10 years earlier, the lung cancer risks were two-fold higher for those who had stopped smoking for coughing or health reasons than for those who had stopped smoking for reasons other than health problems. A decrease in lung cancer risk, although not significant, was found in people who switched from nontiiter brands to filter brands and fmm dark to light tobacco and in smokers who reduced their daily consumption of cigarettes by more than 25% as compared

to smokers who had not changed habits.

Cell type specific, receptor-mediated modulation of growth kinetics in human lung cancer cell lines by nicotine and tobacco-related nitrosamines Schuller HM. Experimenral Oncology Laborarory. Deparnnenr of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37901-1071. Biochem Pharmacol 1989;38:3439-42. The objective of this study was to investigate a potential involvement of nicotinic cholinergic receptors in the mediation of cell type specific biological effects of nicotine and the two tobacco-related nitrosamines N-nitrosodiethylamine (DEN) and 4-(methylnitmsamino)-I-(3-pyridyl)I-butanone (NNK) on human lung cells. Three well differentiated human lung cancer cell lines that have been reported previously to possess ultrastructural and biochemical features of normal pulmonary neuroendocrine cells, Clara cells and alveolar type II cells, respectively, were used for these experiments. The effects of nicotine, DEN, and NNK on cell proliferation and its modulation by establishedantagonisu of nicotinic and muscarinic cholinergic receptors were studied. In the neuroendocrine cell line, nicotine and the two nitrosamines caused a strong stimulation of cell proliferation that was inhibited by antagonists of nicotine cholinergic receptors. In the cell lines with features of Clara cells and alveolar type II cells, nitocine did not stimulate cell proliferation. Both nitmsamines stimulated cell proliferation in the cell line with Clara cell features. This effect was not changed by pre-exposure to cholinergic antagonists. The data suggest a selective uptake of nicotine and the two nitmsamines via nicotinic cholinergic receptors in pulmonary neuroendocrine cells. Transformation of lung cells from inhalation of radon daughters in dwellings: a preliminary study Al-Affan IAM, Haque AKMM. Departmem of Physical Sciences and Scienrifc Computing. South Bank Polyrechnic. London SE1 OAA. Int J Radiit Biol 1989;56:413-22. There is now world-wide concern for the quantification of lung cancer risk due to indoor radon, but the recent estimates are based on epidemiological studies of miners alone. The present attempt is a preliminary studyof thealteration oflung stem cellls irradiated by alpha particles emitted by radon daughters. Local energy deposited has been calculated for alpha particles, emitted from radon daughters lining the mucous layer in the respiratory tracts. This calculation has then been followed by dose evaluation and estimation of transformation of lung cells as a function of age. Mean life span of the stem cells was varied between 5 and 45 years to simulate living conditions in different environments.Thecumulativefractionoftransformedcellsafter4Oand 70 years has been calculated for radonconcentzation in the range 23-230 Bq/m’. Increase of the fraction of transformed cells with radon concentration was exponential. It has been assumed that causes other than radiation increase the rate of cell death of mature and stem lung cells, and hence the turnoverof stem cells to replace them. It is concluded that the rate of transformation of cells is small for low radon concentration even late in age for non-polluted environments. For radon concentrations of 50 and 100 Bq/m3 the fractions of transformed cells are 0.2 and 6 per cent, respectively for an exposure time of 70 years.

Analyses of chromium and nickel in human pulmonary tissue. Investigations in lung cancer patients and a control population under special consideration of medical expertise aspects Raithel HJ, Schaller KH, Akslen LA, Myking AO, Morkve 0, Gulsvik A. Insrilule of Occupational and Social Medicine, University of Erlangen-Nwemberg, D-8520 Erlangen. Int Arch Occup Environ Health 1989;61:507-12. After inhalative occupational exposure to certain compounds containing nickel and chromium (mostly over many years), an accumulation of these metals may occur in the lung tissue. ‘Ihis is of particular importance, both from a toxicological point of view and with regard to expert reports, since certain nickel and chromium compounds may