128 Abstracts/Lung Cancer I1 (1994) 123-150

1945: OR = 1.944,95% CI 0.850-4.445), talc (cumulative exposure > 1000 fibreslml days v never exposed: OR = 1.355,95 96 CI 0.407- 4.515), and asphalt tinnes (cumulative exposure > 0.01 mg/m’days v neverexposed: OR = 1.131,95% C10.468-2.730). For non-malignant respiratory disease, only the smoking variable was significant in the conditional logistic regression analysis (OR = 2.637, 95 % CI 1.146- 6.069). There were raised ORs for the higher cumulative exposure cate- gories for respirable fibres, asbestos, silica, aud asphalt fumes. For both silica and asphalt fumes, ORs were more than double the reference groups for all exposure categories. A limited number of subjects were exposed totinefibres. Thescarcityofcasesandcontrolslimitstheextent to which analyses for line fibre may be carried out. Within those limi- tations, among those who had worked with fine fibre, the unadjusted, unmatched OR for lung cancer was 1.0 (95% CI 0.229-4.373) and for non-malignant respiratory disease, the OR was 1.5 (95% CI 0.336- 6.702). The unadjusted OR for lung cancer for exposure to fine fibre was consistent with that for all mspirable fibres and does not suggest an asso- ciation. For non-malignant respiratory disease, the unadjusted OR for fine fibre was opposite in direction from that for all tespirable fibres. Within the limitations of the available data on line fibre, there is no suggestion that exposure to tine fibre has resulted in an increase in risk of lung cancer. The increased OR for non-malignant respiratory disease is inconclusive. The results of this investigation clearly indicate that for this population, in this place and time, neither respirable fibres nor any of the substances investigated as part of the plant environment are statistically significant factors for lung cancer risk although there are in- creased ORs for exposure to talc and asphalt fumes. Smoking is the most important factor in risk for lung cancer in this population. The situation is less clear for non-malignant respiratory disease. Unlike lung cancer, non-malignantrespiratorydiseaserepresentsaconstellationofoutcomes and not a single well defined end point. Although smoking was the only statistically significant risk factor for non-malignant respiratory disease in this analysis, the ORs for respirable tibres, asbestos, silica, and asphalt tinnesweregreaterthanunityforthehighestexposurecategories. Although the raised ORs for these substances may represent the results of a random process, they may be suggestive of an increased risk and require further investigation.

Increased risk of lung cancer in Japanese smokers with class mu glutathione S-transferase gene def’tciency Kiiara M, KiharaM, NodaK, OkamotoN. DepurtmenrofEpidemiology, Kanagawa Cancer Center, Research Institute, 54-2 Nakao-rho, Asahi- ku, Yokohama 241. Cancer Lett 1993;71:151-5.

Japanese lung cancer patients (n = 121) and community controls (n = 201), both with current smoking history and aged ?4 69, were compared for the rates of class mu glutathione S-transferase (GSTmu) negativegenotypedetectedbypolymerasecbainreaction.Theprevalence of the GSTmu negative genotype was 45.3 96 in the community control group and 68.446, 69.2%. 54.3% and 72.7% in the squamous cell carcinoma, small cell carcinoma, adenocarcinoma and other primary lung cancer groups, respectively. odds ratios adjusted for age, sex composition and smoking index by multiple logistic regression analysis were 2.71 (1.23-5.99), 2.72 (1.11-6.66), 1.33 (0.68-2.60), and 3.27 (0.83-12.81). respectively. These results suggest that smokers with a GSTmu negative genotype are at higher risk for bronchial carcinoma than smokers with positive genotype.

A study of tobacco carcinogenesis. LL Relative potencies of tobacco-specific Knitrosamines as inducers of lung tumours in A/J mice Hoftinann D, Djordjevic MV, Rivenson A, Zang E, Desai D, Amin S. Naylor Dana Inrt Disease Prevention, American Health Foundation, Valhalla, NY 10595. Cancer L&t 1993;71:25-30.

Tobacco-specific N-nitrosamines (TSNA) are formed from nicotine and the minor Nicotiana tabacum alkaloids during tobacco processing andtobaccosmoking.lheTSNAarethemostabundantstmngcarcinogens in smokeless tobacco and in smoke. In this comparative study six TSNA and two major volatile N-nitrosamines of cigarette smoke are assayed for their relative tumorigenicities in strain A/J female mice and for their potential to induce lung tumors. N-nitrosodimethylamine was the most potent inducer of lung adenoma in the A/J mouse model followed in order of decreasing potencies by 4-(methylnitrosamino)-1-(3-pyridyl)- 1-butanone, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, N- nitrosopyrrolidine, N’nitrosonomicotine and N’-nitrosoanabasine. 4(Methylnitrosamino)-I-(3-pyridyl)-1-butanol and 4-(methylnitros- amino)+(3-pyridyl)butyricacidwereinactive. Therelativetumorigenic activities of the tobacco-specific nitrosamines in strain A/J mice compare well with the available data for their relative tumorigenic activities in F344 rats and Syrian golden hamsters.

Basic biology

Comparison of pulmonary 06-methylguanine DNA adduct levels and Ki-ras activation in lung tumors from resistant and susceptible mouse strains Devereux TR, Belinsky SA, Maronpot RR, White CM, Hegi ME, Pate1 AC et al. Laboratory of Molecular Tan’cology. Nat. Inst. ofEnv. Health Sciences, P.O. Box 12233. Research Triangle Park, NC 27709. Mol Carcinog 1993;E: 177-85.

The role of @-methylguanine (@MC) DNA adduct formation and persistence in the formation of 4-(methylnitrosamino)-I-(3-pyridyl)-l- butanone (NNK)-induced lung tumors from resistant C57BL/6 and susceptible A/J mice was investigated. In addition, the frequencies of pulmonary tumor formation and Ki-ras activation were defined in C57BL/6 mice treated with NNK or vinyl catbamate (VC), and the role of the ~53 gene in pulmonary carcinogenesis in these resistant mice was examined. Gneday after treatment with 100 mg/kg NNK, @MG adduct concentrations were twofold to eightfold higher in Clara cells and type II cells than in small cells or whole lungs from both mouse strains. The concentrations of @MG in isolated cells decreased at a similar rate in the two strains of mice. Lung tumors were detected by 27 mo of age in 18% of the C57BL/6 mice after a single 100 mg/kg dose of NNK and in 46% of these mice after a single 60 mgikg dose of VC. In contrast, the tumor incidence in untreated C57BL/6 mice was 4 46. Only one of 22 lung tumors from C57BL16 mice treated with NNK contained an activated Ki-ras gene that was associated with an @MG DNA adduct, whereas previous studies detected activated Ki-ras oncogenes in most of the NNK-induced lung tumors analyzed from susceptible A/J and resistant C3H mice. The small differences in formation and persistence of the @MG adduct in whole lung or isolated lung cells from A/J and C57BL16 strainsdonot account for thedifferences ineither susceptibility for tumor formation or activation of the Ki-ras gene between these strains. In contrast to the low number of NNK-induced tumors with Ki- ras mutations in the resistant mice, 11 of 20 lung tumors from VC- treated mice contained activated Ki-ras genes. Neither p53 tumor suppressor gene mutations nor overexpression of the ~53 protein were detected in spontaneous or chemically induced lung tumors in C57BLl 6 mice. Thus, although Ki-ras activation was detected in some tumors, pathways independent of ras activation and ~53 inactivation also appear to be involved in lung tumorigenesis in this resistant mouse strain.

Nicotine stimulates a serotonergic autocrine loop in human small-cell lung carcinoma Cattaneo MG, Codignola A, Vicentini LM, Clementi F, Sher E. CNRCC, Via Vanvitelli 32,20129 Milan. Cancer Res 1993;53:5566-8.