714 L.R. Ferguson, C.M. Hill and B.C. Baguley 10. Schneider E, Darkin SJ, Lawson PA, Ching L-M, Ralph RK, Baguley BC. Cell line selectivity and DNA breakage properties of the antitumour agent N-[2-(dimethylamino)ethyl]acridine-4-car- boxamide: role of DNA topoisomerase II. EurJ Cancer Clin Oncol 1988,24,1783-1790. 11. Finlay GJ, Baguley BC. Selectivity of N-[2- (dimethylamino)ethylacridine-4-carboxamide towards Lewis lung carcinoma and human tumour cell lines in vitro. EurJ Cancer Clin O ncoll989,25,270- 277. 12. Kaldor JM, Day NE, Band P et al. Second malignancies following testicular cancer, ovarian cancer and Hodgkin’s disease: an inter- national collaborative study among cancer registries. Int J Cancer 1987,39,571-582. 13. Henderson JF. In: Fox BW, Fox M, eds. Anzirumour Drug Resist- ance. Handbook of Experimental Pharmacology, Berlin, Springer- Verlag, Vol. 72,23-39. 14. Wilson WR, Harris NM, Ferguson LR. Comparison of the muta- genic and clastogenic activity of amsacrine and other DNA-interca- lating drugs in cultured V79 Chinese hamster cells. Cancer Res 1984,44,4420-4431. 15. Ferguson LR, van Zijl P, Baguley BC. Comparison of the muta- genicity of amsacrine with that of a new clinical analogue, CI-921. Mutation Res 1988,204,207-217. 16. Ferguson LR, Van Zijl P, Baguley BC. Mutagenicity profiles of newer amsacrine analogues with activity against solid tumours; comparison of microbial and mammalian systems. Eur J Cancer Clin Oncoll989,25,255-261. 17. Zimmermann FK. A yeast strain for visual screening for the two reciprocal products of mitotic crossing-over. Mutation Res 1973, Eur.7 Cancer, Vol. 26, No. 6, pp. 714-718, 1990 Printed m Great Bnrntn 21, 263-269. 18. Ferguson LR, MacPhee DG. Frameshift mutagenesis by acridines in wild type, uvrB and polA strains of Salmonella typhimurium with and without plasmid pKM101. Mutation Res 1984,141,83-88. 19. Maron DM, Ames BN. Revised methods for the Salmonella muta- genicity test. Mutation Res 1983,113,173-215. 20. Ferguson LR. Apparent changes in structure-activity relationships for antimitochondrial effects of 9-anilinoacridines according to Saccharomy ces cerevisiae strain and methodology. Mutation Res 1984,136,223- 231. 21. Baguley BC, Ferguson LR. Inverse correlation between bacterial frameshift mutagenicity and yeast mitochondrial effects of antitu- mour anilinoacridines. Chem-Biol Interactions 1985,56,145-156. 22. DeMarini DM, Doerr CL, Meyer MK, Brock KH, Hazier J, Moore MM. Mutagenicity of m-AMSA and o-AMSA in mammalian cells due to clastogenic mechanism: possible role of topoisomerase. Mutagenesis 1987,2,349-356. 23. Ponunier Y, Zwelling LA, Kao-Shan C-S, Whang-Peng J, Bradley MO. Correlations between intercalator-induced DNA strand breaks and sister chromatid exchanges, mutations and cytotoxicity in Chinese hamster cells. Cancer Res 1985,45,3143-3149. Acknowledgements-Supported by the Cancer Society of New Zealand, its Auckland Division, and the Medical Research Council of New Zealand. The authors are grateful to Pamela Turner and Susan O’Rourke for help with the microbial assays, and to Lynden Hull for secretarial help. 0277-537919053.00 + 0.00 0 1990rergamo?lPresspk Cigarette Smoking and Bladder Cancer Barbara D’Avanzo, Eva Negri, Carlo La Vecchia, Annagiulia Gramenzi, Cosetta Bianchi, Silvia Franceschi and Peter Boyle The relation between cigarette smoking and risk of bladder cancer was analysed in a case-control study in Northern Italy of 337 cases of histologically conlirmed invasive bladder cancer and 392 controls admitted to the same network of hospitals with acute, non-neoplastic, non-urological conditions. Compared with never-smokers, the multivariate relative risk (RR) was 1.9 (95% confidence interval, CI 1.2-3.1) for ex-smokers and 3.3 (95% CI 2.2-5.0) for current smokers. The risk was directly and significantly related to duration of smoking (RR 3.5 for 30 years or more) and dose (RR 3.9 for 20 cigarettes per day or more), and consistent among strata of sex and age (though the RRs were systematically higher at older ages). Smokers of black tobacco only had a RR of 3.7, compared with 2.6 for smokers of blond cigarettes or mixed types . The interaction between tobacco and several occupations associated with bladder cancer risk fitted an additive rather than a multiplicative model: compared with non-exposed never-smokers, RR was 2.5 for exposed non-smokers, 2.8 for non-exposed smokers and 3.7 for occupationally exposed smokers. EurJCancer, Vol. 26, No. 6, pp. 714-718,199O. INTRODUCTION Italian case-control study found a strong association between BLADDER CANCER is a known tobacco-related neoplasm, but the cigarette smoking and bladder cancer risk, with RR of 5.1 for strength of the association is uncertain: the relative risks (RR) smokers and of over 10 for heavy smokers (30 or more cigarettes for smokers compared with non-smokers ranged between 1.4 per day) [3]. The proposed explanation for these elevated risks and 2.9 in eight cohort studies, and the range of variation was in an Italian population was the high frequency of dark tobacco even larger (1.2-7.3) in twenty case-control studies [l-12]. An smoked in the past in Italy [3, 41. We present data from another