Lung Cancer, 8 (1992) 119-000 0 1992 Elsevier Science Publishers B.V. All rights reserved 0169-5002/92/$05.00

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ABSTRACTS

Prevention Mainstream aad environmental tobacco smoke Gori GB, Mantel N. The Health Policy Center, 6704 Barr Road, Bethesda MD 20816. Regul Toxic01 Pharmacol 1991;14:88-105.

Environmental tobacco smoke (ETS) is derived from cigarette smoldering and active smoker exhalation. Its composition displays broad quantitative differences and rediwibutions between gas and respirable suspended particulate (RSP) phases when compared with the mainstream smoke (MSS) that smokers puff. This is because of differ- ent generation conditions and because ETS is diluted and ages vastly more than MSS. Such differences prevent a direct comparison of MSS andETSandtheirbiologicactivities. However,evena.ssumingsimilari- ties on an equal mass basis, ETS-RSP inhaled doses are estimated to be between lO,OOO- and 100,000-fold less than estimated average MSS- RSP doses for active smokers. Differences in effective gas phase doses arc expected to be of similar magnitude. Thus the average person exposed to ETS would retain an annual dose analogous to the active MSS smoking of considerably less than one cigarette dispersed over a l-year period. By contrast, consistent epidemiologic data indicate that active smoking of some 4-5 cigarettes per day may not be associated with a significantly increased risk of lung cancer. Similar indications also obtain for cardiovascular and respiratory diseases. Since average doses of ETS to nonsmoking subjects in epidemiologic studies are several thousand times less than this reported intake level, the marginal relativerisksoflungcancerandotherdiseasesatnibutedtoETS insome eptdemiologic studies are likely to be statistical artifacts, derived from unaccounted confounders and unavotdable bias.

Smoking-attributable cancer mortality in 1991: Is lung cancer now the leading caase of death among smokers in the United states? Shopland DR, Eyre HJ, Pechacek TF. Smoking and Tobacco Control Program, Executive Plaza North, Narionnl Institutes of Health, 9ooO RockvillePike.Bethesda.MD20892. JNatlCancerInst 1991;83:1142- 8.

Findings from the new American Cancer Society prospective study of 1.2 million men and women indicate that mortality risks among smokers have increased substantially for most of the eight major cancer sites causally associated with cigarette smoking. Lung cancer risk for male smokers doubled, while the nsk for females increased more than fourfold. On the basis of the new American Cancer Society relative risks, we project that cigarette smoking alone will contribute to slightly more than 157 OtXl of the 5 14 000 total cancer deaths expected to occur in the United States in 1991. Overall, smoking directly contributes to 21.5% of all cancer deaths in women but 45% of all cancer deaths in men. It would also appear that lung cancer has now displaced coronary heart disease as the single leading cause of excess mortality among smokers in the United States.

Asbestos-induced lung cancer - The problems entailed in occupa- tional disease litigation Borsch-GaJetke E. lnstitrct fur Arbeitsmedizin, Marienplatz 2. 4630 Bochum 1. Arbeiumed. Sozialmed Praventivmed 1991;26:351-6.

The presence of an asbestos induced bronchial carcinoma act. to No. 4104 of the BeKV must be affirmed, when me following prerequisites are met: 1) when there is sufficient exposure to asbestos Bbres. This must be assumed at least, if the assessment of asbestos fibre years amounts to 20 * 5.2) A bronchial carcinoma can be diagnosed together with so called ‘bridge symptoms’. These may be a) asbestos induced pulmonary fibrosis at least with the proportions of minimum asbestosis and/orb) asbestos induced pleural alterations. In case of clarification by differential diagnosis, it is essential to make acomputerized tomogram of the thorax. The question is pending whether and on what conditions

abronchialcarcinomamustberecognizedincaseofsufficientexposure to asbestos fibres act. to paragraph 551, para 2 German Nattonal Insurance Code

Composition of popular tobacco products in Thailand, and its relevance to disease prevention Mitacek EJ, Bronnemann KD, Polednak AP, Hoffmann D, Suttajit M. Life SciencesDivision, New YorkInstitute of Technology. P.O. Box 170, Old Westbury. NY 11568. Prev Med 1991;20:7&1-73.

Background. This report presents new findings on the composition of the three best-selling brands of commercially produced Thai cigarettes, representing about 80% of market share in Thailand, and six best- selling tobacco pmducts, including hand-rolled cigarettes and cigars. Results. With one exception, all Thai cigarettes yielded higher levels of tar and nicotine than U.S. brands sold in Thailand. High levels of tar, nicotine, and carbon monoxide (CO) were found in the smoke of popular Thai cigars (Khiyo) and Burmese cigars sold in Thailand. All tobacco products tested were ranked in order of smoke yields of tar (cigarettes, 4.5 to 40.8 mg/cigarette), nicotine (0.19 to 5.77 mg/ cigarette), and CO (3.1 to 9.5 mg/cigarette). The labels ‘very strong,’ ‘strong,’ and ‘mild,’ used in rating the tobacco quality by the growers inThailand, werenot found toreflect the relative nicotineand tar yields. From 1985-1990, per capita consumption of cigarettes in Thailand increased 1.4-fold. Conclusion. This report provides information that may prove helpful in the evaluation of the tar, nicotine, and carbon monoxide yields of cigarettes and cigars in Thailand compared with levels in U.S. cigarettes. It is our goal to offer the scientiftc basis for voluntary and/or regulated reduction of the smoke yields of tobacco products in Thailand.

Formation of benzo[a]pyrene-DNA adducts in blood monocytes from lung cancer patients with a familial history of lung cancer Nowak D, Meyer A, Schmidt-Preuss U, Gatzemeier U, Magnussen H, RudigerH.W. Arbeitsgruppe Toxikogenetik. OrdinariatfurArbeitsme- dizin, Universitat Hamburg, Adolph-Schonfelder-Strosse 5, W-2000 Hamburg 76. J Cancer Res Clin Gncol 1992;118:67-71.

The in vitro formation of benzo[a]pyrene-DNA adducts was deter- mined in peripheral blood monocytes of 22 lung cancer patients with at least one fmt-degree relative with lung cancer and compared to results obtained in 30 healthy controls. In patients, the mean (SEM) adduct formation was 2.8 (0.3) fmol/pg DNA as compared to 2.1(0.1) fmol/)rg incontrols(p~O.O5).and itwasindependentofageand smoking habits. These findings support the hypothesis that carcinogen-DNA adduct formation may be one factor of a constitutionally enhanced lung cancer risk.

Epidemiology and etiology

Lung cancer incidence among patients with beryllium disease: A cohort mortality study Steenland K, Ward E. NIOSH, Mailstop R13,4676 Columbia Pkwy.. Cincinnati, OH 45226. J Nat1 Cancer Inst 1991;83:1380-5.

We have conducted a cohort mortality study on 689 patients with beryllium disease who were included in a case registry. An earlier mortality study on 421 of these patients was limited to males and msulted in a determination of a nonsignificant twofold lung cancer excess based on only seven lung cancer deaths. We have extended this earlier study by including females and by adding 13 years of follow-up. Comparison of the 689 beryllium disease patients with the U.S. popu- lation resulted in a lung cancer standardized mortality ratio (SMR) of 2.08 (95% confidence interval = 1.33-2.89) based on 28 observed lung

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cancer deaths. Adjustment for smoking did not change these results. All causes of mortality were also significantly elevated (SMR = 2.19), largely because of the very high rate of deaths due to pneumoconioses (primarily beryllium disease) (SMR = 34.23; 158 deaths). No other causes of death were significantly elevated. The excess of lung cancer was consistent for both sexes and did not appear to increase with duration of exposure to beryllium or with time elapsed since fist exposure to this element. The case registry included those with acute beryllium disease, which resembles a chemical pneumonitis. and those with chronic beryllium disease, which resembles other pneumoco- nioses. The lung cancer excess was more pronounced among those with acute disease (SMR = 2.32) than among those with chronic disease (SMR = 1.57).

Long cancer and hydrogen chloride exposure: Results from a nested case-control study of chemical workers BondGG,FioresGH,StaffordBA,OlsenGW.DepartmenrofEpidemi- ology. Health and Environmemo Sciences, Dow Chemical Cornpony, 1803 Building, Midland, MI 48674. J Occup Med 1991;33:958-61.

Thereare few epidemiologic dataavailable to address the question of potential carcinogenic effects of hydrogen chloride (HCl) exposure on humans. An opportunity arose to augment a nominal HCl exposure classification that had been done earlier for a nested case-control study of lung cancer among a cohort of chemical manufacturing employees. Working from fist-hand knowledge of the relevant chemical processes and limited HCl monitoring data, a cenified industrial hygienist esti- mated average exposures for each of the job assignments of 308 lung cancer cases and 616 comparison workers. The risk of lung cancer was then analyzed in relation to several measures of HCI exposure, includ- ing duration, a cumulative exposure score, highest average exposure, and btency. None showed evidence of an association between HCl exposure and lung cancer. This is consistent with the limited rodent bioassay data, which also failed LO find a tumorigenic response from HCl. Thus, even at high level occupational exposures (up to 3000 pg/m3 for several years) there is no evidence that HCI is a human carcinogen.

Advances in cancer biomarkers as applied to chemical exposures: The ras oncogene and ptl protein and pulmonary carcinogeaesis Brandt-Rauf PW. Division of Environmenral Sciences, Deparfmenr of Medicine, andComprehensive Cancer Center, Columbia University, 60 Haven Ave. New York, NY 10032. J Occup Med 1991;33:951-5.

Pulmonary carcinogenesis due to occupational and environmental exposures to chemical carcinogens such as polycyclic aromatic hydro- carbons presents an interesting model for study of possible oncogene- related cancer biomarkers. Polycyclic aromatic hydrocarbons are im- portant respiratory carcinogens and have been shown to cattse specific mutational lesionstbatcan lead totbeactivation of theras oncogeneand expression of its p21 protein product; ras oncogene activation and p21 expression frequently are detected in human lung cancers. In addition, the p21 protein is detectable via immunoblotting techniques in the serum of lung cancer patients and in selected persons in exposed worker cohorts at risk for the development of lung cancer. Thus, the ras oncogene and p21 protein may be useful biomarkers for monitoring pulmonary carcinogenesis in exposed populations.

Sensitivity and specificity of long cancer screening in Osaka, Japan Sobue T. Suzuki T. Matsuda M. Horai T. Kajita A. Kuriyama K et al. Department of Field Research, Center for Adult Diseases, Osaka, l-3- 3 Nakmichi. Higashitwi-ku, Osaka 537. Jpn J Cancer Res 1991;82: lC49- 76.

Sensitivity and specificity were evaluated for lung cancer screening conducted at 8 municipalities in Osaka Prefecture during 1981-1985. As a screening policy, all attendants were examined by miniature chest X-ray, and the high-risk group, defined as those who smoked cigarettes or had bloody sputum, were also examined by 3-day pooled sputum

cytology. A total of 33,599 screening tests for 19,028 people who were 40 years old or more at the time of screening were conducted, resulting in 33,490 miniature chest X-ray examinations for 18,992 people and 11,420 sputum cytologies for 7,070 people. As a result 43 lung cancer cases were detected. All test-negatives were followed by means of record linkage with the files of the Osaka Cancer Registry up to the end of 1986. There were 24 cases who were diagnosed as having lung cancer without having given a positive screening result in 1981-1986. Assum- ing the preclinical detectable phase of lung cancer to be one year uniformly, the sensitivity and specificity for the lung cancer screening wereestimated to be71.6% and95.3%, respectively. The feasibility of increasing the sensitivity is discussed.

Carcinogen metabolism and DNA addocts in human long tissues as affected by tobacco smoking or metabolic phenotype: A case- control study on lung cancer patients Bartsch H. Petmzzelli S, De Flora S, Hietanen E. Camus A-M, Casteg- nary Met al. International Agency for Research on Cancer, 150 Cours Albert-Thomas, F-69372 Lyon Cede% 08. Mutat Res Fundam Mol Mech Mutagen 1991;250:103-14.

Individual variations in activity of pulmonary enzymes that metabo- lizetobacco-derived carcinogens may affectan individual’scancer risk from cigarette smoking. To investigate whether some of these enzymes (e.g.,cytochromeWSOIA-related) can serve asmarkers forcarcinogen- induced DNA damage accumulating in the lungs of smokers, non- tumorous lung tissue specimens were taken during surgery from middle- agedmen witheitberlungcancer(n=54)ornowneoplastic lungdisease (n = 20). Phase I (AHH, ECDE) and phase II (EH, UDPGT. GST) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchml tissues: some samples were analyzed for DNA adducts, using 3*P-postlabeling. Data analysis Of subsets or the whole group of patients yielded the following results. (l)Pha~IandIIdrug-metabolizingenzyme(AHH,EH,UDPGT,GST) activities in histologically normal surgical specimens of lung paren- chyma were correlated with the respective enzyme activities in bron- chial tissues of the same subject. (2) In lung parenchyma, enzyme (AHH,ECDE,EH,UDPGT)activitiesweresignificantly andpositively related to each other, implying a similar regulatory control of their expression. (3) Mean activities of pnmonary enzymes (AHH, ECDE) were significantly (2- and 7-fold, respectively) higher in lung cancer patients who had smoked within 30 days before surgery (except GST, which was depressed) than in cancer-free subjects with a similar smoking history. (4) In the cancer patients, the time required for AHH, EH and UDPGT activities to return to the level found in non-smoking subjects was several weeks. (5) Bronchial tree and peripheral lung parenchyma preparations exhibited a poor efficiency in activating promutagens to bacterial mutagens in Salmonella. However, they decreased the mutagenicity of several direct-acting mutagens, an effect which was more pronounced in tissue from recent smokers. GSH con- centration and GST activity were positively correlated with mutagen inactivation in the same sample. (6) In recent smokers, AHH activity in lung parenchyma was positively correlated with the level of tobacco smoke-derived DNA adducts. (7) Pulmonary AHH and EH activity had prognostic value in tobacco-related lung cancer patients. (8) An en- hanced level of pro-oxidant state in the lungs was associated with recent cigarette smoking. Malondialdehyde level in lung parenchyma was associated with the degree of small airway obstruction, suggesting a common free radical-mediated pathway for both lung cancer induction and small airway obstruction. These results demonstrate the pro- nounced effect of recent cigarette smoke exposure on pulmonary xenobiotic metabolism and lipid peroxidation and lend further support to the hypothesis that the inducibility of pulmonary AHH activity (cytochrome P450IAl levels) in tobacco smokers is assocaited with lung cancer risk. Results on DNA adducts in smokers’ lung tissue may help to explain why a certain metabolic phenotype accumulates more

DNA damage in lung cells.