Silica exposure, silicosis, and lung cancer: A necropsy study

123 experiences according to a structured questionnaire. A strong association between smoking habits and lung cancer risk was found for all histological subgroups. Relative risks for those who had smoked daily daring at least one year ranged between 3.1 for adenocarcinoma to 33.7 for small cell carcinoma in a comparison with never-smokers. All histological types showed strong dose-response relationships for average daily cigarette consumption, duration of smoking, and cumulative smoking. There was no consistent effect of parental smoking on the lung cancer risk in smokers. Only 38 cases had never been regular smokers and the risk estimates for exposure to environmental tobacco smoke were inconclusive. The high relative risks of small cell and.squamous cellcarcinomaassociated with smoking may have implications for risk assessments regarding passive smoking. Lung cancer mortality and silicosis in Quebec, 1938-85

Infante-Rivard C, Armstrong B, Peticlerc M, Cloutier L-G, Thenault G. School of Occupa&mal Health, McGill Universiry, 1130 Pine Avenue War, Monlreal, Que. H3A ZA3. Laocet 1989;2:1504-7. Men who had received compensation for silicosis in Quebec between 1938and 1985werestudieduptotheendof 1986toestimateriskoflung cancer mortality. Particular attention was paid to selection biases inherent in the study of such workers. Age-specific and calendar-yearspecific mortality rates of Quebec men from 193 1to 1985 were.used for comparison. Risk of death from lung cancer in men who had received compensation for silicosis was more than 3 times higher than expected; silicosis may be a strong risk factor for lung cancer mortality.

Smoking and lung cancer mortality io Japanese men: Estimates for dose and duration of cigarette smoking based on the Japan Vital Statistics data Mizuno S, Akiba S. Departmenl of Baristics. Radialion Eflects Research Foundation, 5-2. Hijiyama Park. Minomi-ku, Hiroshima 732

Jpn J Cancer Res (Gann) 1989;80:727-3 I. For the purpose of understanding human carcinogenesis and making a quantitative prediction of lung cancer mortality in a general population of Japanese males, we evaluated a statistical model which assumes lung cancer mortality to be proportional to the 4.5th power of the effective duration of cigarette smoking among smokers and to the 4th power of age among nonsmokers, using Japan Vital Statistics data. For the male birth cohorts aged 30-69 in 1965 in the age range of 40-79, studied by quinquennial calendar time intervals from 1955 to 1985, it was found that, (i) for nonsmokers, the estimated lung cancer mortality rate was comparable to the rates reported in the US or Britain, assigning 20 to 25% proportions of nonsmokers, (ii) for smokers, the estimated duration of smoking was shorter than would be expected from the age when smoking was started according to various epidemiological surveys, and (iii) the estimated average numbers of cigarettes smoked per day by smokers were similar to those obtained by epidemiological studies, when these were estimated by incorporating a part of Doll and Pete’s dose-response relationship. Also discussed is the possibility of assessing lung cancer mortality risk for Japanese male smokers by means of the statistical model, _ x(cigarettes smoked per day + O)x(age(age started smoking)- gammaG5.

Quantitative evaluation of the radon and lung cancer association in a case control study of Chinese tin miners Lubin JH, Qiao Y-L, Taylor PR et al. Epidemiology Methods Secrion, Bioswisdcs Branch, Division of Cancer Eriofogy, Nalional Cancer Insrimte. Rockville, MD 20892. Cancer Res 1990;50:174-80.

Studies of underground miners have consistently shown an increased riskof lungcancer withcumulativeexposure toradow222anditsdecay products. Although the deleterious effects of high radon exposure are clear, questions regarding the shape of the exposure-response relationship, and the effects of time factors such as attained age, time since

exposure and early age at first exposure, the effect of exposure rate, and the joint association of radon exposure and tobacco use have not yet been fully clarified. This report considers these questions by fitting various models for the relative odds of &ease to 74 male lung cancer cases who were diagnosed between 1981 and 1984 and were alive in 1985 and an equal number of controls. All subjects are current or past employees of the Yunnan Tin Corporation, Gejiu City, China, who reside in the local area. Workers were interviewed to obtain informaoon on work history, from which radon exposure in cumulative working level months and arsenic exposure were estimated, and on tobacco use. Results indicate that excess relative risk increases by 1.7% per cumulative working level month [95% confidence interval (0.5, 5.4)]. The linear exposure response relatIonship significantly declines with year since last radon exposure (P=O.O2).The risk trend also declines with increasing exposure. rate (P=O.OOl), indicating that long duration of exposure at a low rate may be more deleterious than short duration of exposure at a high rate. A unique aspect of this study population is the wry early ages at first radon exposure for many of the workers, about 37% of the radon-exposed workers were fist exposed under the age of I3 years. The analysis shows no modification of the radon lung cancer relationship with age at first exposure. Thcsc patterns of risk with radon exposure are generally consistent with those reported in the recent National Academy of Sciences’ Biological Effects of Ionizing RadiationsIVreport.Theprimary methodof tobaccoconsumptionin thisarea of China is by waterpipe. Long cancer risk increases with pipe-years of use. The joint analysis of tobacco use and radon exposure. supports the Biological Effects of Ionizing Radiations IV conclusion that the most likely model is between additive and multiplicative. The variations of the radon lung cancer relationship by years since last exposure and exposure rate are not affected by adjustment for arsenic exposure. Epidemiologic survey on lung cancer with respect to cigarette smoking and plant diet Sakai R. Deportmenr of Epidemiology, School of Health Sciences, Ryukyu University, 207 Uehara, Okinawa 903-01. Jpn J Cancer Res

(Gann) 1989;80:513-20. This case-control study of lung cancer was based on a cross-sectional questionnaire survey of Inpatients at 5 general hospitals in Okinawa, Japan, from 1982 to 1987. The purpose of the study was to clarify the relations of lung cancer to cigarette smoking and plant diet. Ingestion frequencies of I7 major dietary plants and/or herbs were obtained by means of a questionnaire interview. As eligible subjects for a casecontrol analysis, there were 673 respondents aged over 30 years with clear smoking history, age, sex and diagnosis. Psychiatric patients were excluded. Odds ratios of newly diagnosed lung cancer were calculated by the Mantel-Hacnszel procedure. A pair consisted of a case and two controls which were selected randomly by using multivariate caliper matching. Sixty-four pairs matched for age (+S) and sex showed a significantly high odds ratio of 2.9 (P < O.ooO5). However, three male groups who were categorized by the number of cigarettes smoked did not exhibit dose-dependency of lung cancer on smoking. Lung cancer was more prevalent in ex-smokers than in current smokers. Case control analyses by male generations revealed that lung cancer incidence was age-dependent, and there was a clear dose-response rclationship between smoking and long cancer in males in their sixties. A casecontrol analysis of each of 17 edible plants based on 44 pairs who were matched for age (f5). sex and smoking history demonstrated that the odds ratio of aloe (Aloe arborescens MILL var. Natalensis BERGER) was 0.5 (P < 0. I), suggesting that the aloe may prevent human carcinogenesis at various sites. Silica exposure, silicosis, and lung cancer: A necropsy study Hesscl PA, Sluis-Cremcr GK, Hnizdo E. Epidemiology Research Lmit, P.O. Box 4584, Johannesburg 2000. Br J Ind Med 1990;47:4-9.

Recent studies of the association between lung cancer and silicosis

124 and silica dust have heen inconclusive; some showing positive association and some showing none. The present study matched 231 cases of lung cancer with 318 convols by year of birth. Subjects were selected from the necropsy records of the National Centre.for Occupational Health. Data on intensity and duration of exposure to silica dust were obtained from personnel records. Presence or absence of lung cancer and the presence and severity of silicosis of the parenchyma, pleura, and hilar glands were documented from necropsy reports. Smoking data were abstracted from records of routine examinations. No case-control differences were noted for any of the exposure indicators including cumulative dust exposure, total dusty shifts, weighted average intensity of exposure, total underground shifts, and shifts in high dust. Similarly, no association was found between lung cancer and the presence or severity of silicosis of any site. Stratified analyses showed neither significant nor suggestive eends when case-conuol comparisons for silicosis were examined by level of dust exposure or smoking. Reasons for disparity between these results and those of some other studies may include concomitant exposures to radon daughters, asbestos, diesel emissions, and cigarette smoking; idiosyncracies of the compensation process; and the possibility of a threshold in the relation(s).

Basic biology Transcription factors and recessive oncogenes in the pathogenesis of human lung cancer Minna ID, Schutte J, Viallet I et al. NCI-Navy Medical Oncology Branch, Medicine Branch, Nalionul Cancer Institute, Naval Hospital. Bethesda, MD 20814. Int J Cancer 1989;Suppl. 4~32-4. Natural killer cells are characterized by the lack of CD3/TCR molecules and by the expression of CD16 and CD56(NKHl or Leu 19) surface antigens. In addition to their ability to lyse certain tumor target cells, they release lymphokines including tumor necrosis factor and interferon gamma. Another unexpected functional capability of at least some NK cells is the ability to specifically recognize and lyse certain normal allogeneiccells @‘HA-inducedblasts). MAbsdirected to CD2 or to CD 16 surface molecules induces triggering of NK cells leading to target cell (~815) lysis in a redirected killing assay. Importantly, different from unduction of T cell activation, single anti-CD2 MAbs were sufficient to trigger NK cell function. Another MAb (GL183) inducing NK cell triggering recognized a novel surface molectdes expressed on 2O-50% of resting or cultured NK cells. Clones GL183+ cells displayed a variable degree of cytolytic activity against a number of human target cells of different histotype; moreover, this activity was strongly enhanced by the addition of GL183 MAb. On the other hand, GL183 MAb inhibited lysis of murine lines (including P815). Thus on P815 target cells GL183 MAb has an effect antithetical to that of other stimuli including PHA, anti CD2 or anti-CD16 MAbs. GL183 MAb, added simultaneously to one or another of the stimuli above, strongly inhibited the target cell lysis induced by these stimuli. Thus, GL183 may represent an important molecule in the process of activation/ regulation of phenotypically-defined NK cell subsets. Patients with different lung cancers show normal expression of fra@)(p143) in apbidicolin-treated lymphocyte cultures Porfiio B, Paladini P, Maccherini M, Gotti G, Cintorino M, De Marchi M. Depanment ofMedical Genetics. Universilyof Siena, Siena. Cancer Genet Cytogenet 1989;43:95-101. Among common fragile sites, fra(3)@14.2) is the most expressed either spontaneously or after treatment with aphidicolin (APC) in lymphocyte cultures. Because recurrent chromosomal abnormalities involving the short arm of chromosome 3 in tumor tissue are present in various malignancies, including hmg cancer, the induction of f&3&114.2) elicited by AFC was investigated with the aim of detecting possible interindividual polymorphism in its expression that might be relevant to predisposition toward cancer-related events. Thirty-four patients af-

fected with various lung cancers (14 squamous cell carcinomas, 13 adenocarcinomas, and seven small cell carcinomas) and 14 controls (patients undergoing routine follow-up after coronary by-pass) were included in this study. The frequency of fra(3)@14.2) expression was not significantly different among the patients grouped either by disease or by sex and age. It was estimated that fra(3)@14.2) accounts for about 20% of total breakage in APC-treated lymphocyte. cultures from the general population. Antigens associated with multidrug resistance in H69AR, a small cell lung cancer cell line Miiski SEL, Cole SPC. Deparimenf of Oncology, Queen’s University, Kingston, 0111.K7L 3N6. Cancer Res 1989:49:5719-24. In a previous study (S.E.L. Mirski et al., Cancer Res., 47: 2594-2598, 1987). we described the derivation of a multidrug-resistant small cell lung cancer cell line, H69AR. Tbe H69AR cell line does not overexpress P-glycoprotein and is therefore a useful model for the investigation of alternate mechanisms of drug resistance. In this paper we report lheproductionandpreliminarycharacterizationofsixmurinemonoclonal antibodies (MAbs) which react selectively with the H69AR cell line compared to its drug-sensitive parent cell line, NCI-H69. One of these antibodies, MAb 2.54, detects a cell surface epitope and reacts with multiple proteins of molecular weight 24,500-34,500 on immtmoblots. Non-cell surface membrane-associated epitopes are detected by the otherfiveantibodies, MAbs3.50,3.80,3.177,3.187,and3.186. MAbs 3.50and3.186immunoprecipitateantigensofmolecular weight55.000 and 36&Q respectively, while MAbs 3.80, 3.177, and 3.187 aI1 precipitateamolecularweight47,000protein,suggestinglhat they may detect epitopes on the same antigen. The epitope detected by all six antibodies are present on greater than 80% of H69AR cells, as determined by flow cytomeiry. With the exception of MAb 2.54, the MAbs cross-react in an enzyme-linked immunosorbent assay with the multidmg-resistant human fibrosarcoma cell line HT108O/DR4. Thus, these MAbs react with two drug-resistant cell lines derived from different tumor types in which overexpression of P-glycoprotein is undetectable. These MAbs may detect novel markers for drug resistance and thus may have potential diagnostic or therapeutic value. Inhibition of growth and modulation of gene expression in human lung carcinoma in athymic mice by site-selective S-Cl-cyclic adenosine monophosphate Ally S, Clair T, Katsaros D et al. Cellular Biochemistry Section, Laboratory of Tamorlmmanology andBiology, National Cancer Institute, Notional Institutes of He&h, Be&esda, MD 20892. Cancer Res

1989;49:5650-5. Site-selective cyclic AMP (CAMP) analogues inhibit growth and induce changes in morphology in a spectrum of human cancer cell lines (D. Katsaros et al., FEBS Lett., 223:97, 1987). The cellular evenIs underlying such effects of CAMP analogues include differential regulation of type I versus type II CAMP-dependent protein kinase isozymes (S. Ally et al., Proc. Natl. Acad. Sci. USA, 85: 6319, 1988). Infusion (i.p.) of 8-Cl-CAMP, the most potent site-selective CAMP analogue, for 7 days producedregression of LX-l lung carcinoma in athymic mice in a dose-dependent manner. The tumor regression correlated with the changing levels of CAMP receptor proteins, RI(a) and RII(a), the regulatory subunits of CAMP-dependent protein kinase type I and type II, respectively. By photoaffinity labeling with 8-N,-[3*P]cAMP and immunoblotting with a monospecific anti-RI1 antibody, RIa) (M(r) 49,COO)and RII(l7) (M(r) 51,ooO) were identified in the untreated control tumors. 8-C& treatment induced a rapid increase of both RI(a) and RII(l3) in tumor cytosols and Iran&cations (within 1 h) of only RII(l3)from the cytosol to the nucleus. RII(8) in both cytosols and nuclei remained elevated during 8-Cl-CAMP treatment, whereas RI(a) inthecytosolsgraduallydecreasedwith timeoftreaunentafterilsinitial transient increase. Northern blot analyses demonstrated that the RII(B) mRNA level increased within 6 h of 8.Cl-CAMP treaunent and re-