Mutagenicity of urine from nurses handling cytostatic drugs, influence of smoking

  • R. P. Bos
  • A. O. Leenaars
  • J. L. G. Theuws
  • P. Th. Henderson
Original Papers


Mutagenicity towards Salmonella typhimurium TA 100 of urine from smoking nurses, who were occupationally involved in the treatment of patients with cytostatic drugs, was significantly increased in comparison with that of smoking control subjects. Mutagenicity towards Salmonella typhimurium TA 100 was not increased in exposed non-smokers when compared to control non-smokers. In smoking subjects urinary mutagenicity appeared increased towards Salmonella typhimurium TA 1538 in the presence of S-9 mix.

Rats pretreated with Aroclor 1254 showed higher mutagenicity in their urine than untreated rats after cyclophosphamide administration. Therefore, the synergistic effect of smoking might be due in part to induction of enzymes involved in the mutagenic activation of cytostatic drugs. Further, the animal experiments showed that cyclophosphamide (the most frequently used mutagenic cytostatic drug) can be absorbed after oral or percutaneous administration. Therefore, it is not excluded that differences in working hygiene between smokers and non-smokers also play a role.

Key words

Mutagens/urine Salmonella typhimurium Antineoplastic agents Cyclophosphamide Smoking Environmental exposure 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ames BN, McCann J, Yamasaki E (1975) Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test. Mutat Res 31:347–364Google Scholar
  2. Balbinder E, Reich CI, Shugarts D, Keogh J, Fibiger R, Jones T, Banks A (1981) Relative mutagenicity of some urinary metabolites of the antitumor drug cyclophosphamide. Cancer Res 41:2967–2972Google Scholar
  3. Benedict WF, Baker MS, Haroun L, Choi E, Ames BN (1977) Mutagenicity of cancer chemotherapeutic agents in the Salmonella/microsome test. Cancer Res 37:2209–2213Google Scholar
  4. Boobis AR, Brodie MJ, Bulpitt CJ, Davies DS (1979) Environmental factors affecting monooxygenase activity of microsomal fractions of human liver biopsies. Br J Pharmacol 66: 426P-427PGoogle Scholar
  5. Doorn R van, Bos RP, Leijdekkers Ch-M, Wagenaars-Zegers MAP, Theuws JLG, Henderson PTh (1979) Thioether concentration and mutagenicity of urine from cigarette smokers. Int Arch Occup Environ Health 43:159–166Google Scholar
  6. Falck K, Gröhn P, Sorsa M, Vainio H, Heinonen E, Holsti LR (1979) Mutagenicity in urine of nurses handling cytostatic drugs. Lancet 1:1250–1251Google Scholar
  7. Falck K, Sorsa M, Vainio H (1980) Mutagenicity in urine of workers in rubber industry. Mutat Res 79:45–52Google Scholar
  8. Falck K, Sorsa M, Vainio H (1981) Use of the bacterial fluctuation test to detect mutagenicity in urine of nurses handling cytostatic drugs. Mutat Res 85:236–237Google Scholar
  9. Hannan MA, Recio L, Deluca PP, Enoch H (1981) Co-mutagenic effects of 2-aminoanthracene and cigarette smoke condensate on smoker's urine in the Ames Salmonella assay system. Cancer Lett 13:203–212Google Scholar
  10. Harris CC (1976) The carcinogenicity of anticancer drugs: a hazard in man. Cancer 37:1014–1023Google Scholar
  11. Joosting PE (1981) Wat is de betekenis van arbeidshygiënische ‘normen’ met en zonder tabak? T Soc Geneesk 59:762–771Google Scholar
  12. Jusko WJ (1979) Influence of cigarette smoking on drug metabolism in man. Drug Metab Rev 9:221–236Google Scholar
  13. Leopold WR, Miller EC, Miller JA (1979) Carcinogenicity of antitumor cis-platinum(II) coordination complexes in the mouse and rat. Cancer Res 39:913–918Google Scholar
  14. Matheson D, Brusick D, Carrano R (1978) Comparison of the relative mutagenic activity for eight antineoplastic drugs in the Ames Salmonella/microsome and TK+/- mouse lymphoma assays. Drug Chem Toxicol 1:277–304Google Scholar
  15. Minnich V, Smith ME, Thompson D, Kornfeld S (1976) Detection of mutagenic activity in human urine using mutant strains of Salmonella typhimurium. Cancer 38:1253–1258Google Scholar
  16. Nagao M, Yahagi T, Honda M, Seino Y, Kawachi T, Sugimura T, Wakabayashi K, Tsuji K, Kosuge T (1977) Comutagenic actions of norharman derivatives with 4-dimethylaminoazobenzene and related compounds. Cancer Lett 3:339–346Google Scholar
  17. NIOSH, Current intelligence bulletin. Center for disease control, US dept. of health, education and welfare. No. 31, Feb. 5th 1979Google Scholar
  18. Norppa H, Sorsa M, Vainio H, Gröhn P, Heinonen E, Holsti L, Nordman E (1980) Increased sister chromatid exchange frequencies in lymphocytes of nurses handling cytostatic drugs. Scand J Work Environ Health 6:299–301Google Scholar
  19. Pak K, Iwasaki T, Miyakawa M, Yoshida O (1979) The mutagenic activity of anti-cancer drugs and the urine of rats given these drugs. Urol Res 7:119–124Google Scholar
  20. Seino Y, Nagao M, Yahagi T, Hoshi A, Kawachi T, Sugimura T (1978) Mutagenicity of several classes of antitumor agents to Salmonella typhimurium TA98, TA 100, and TA92. Cancer Res 38:2148–2156Google Scholar
  21. Waksvik H, Klepp O, Brøgger A (1981) Chromosome analyses of nurses handling cytostatic agents. Cancer Treat Rep 65:607–610Google Scholar
  22. Wheeler LA, Saperstein MD, Lowe NJ (1981) Mutagenicity of urine from psoriatic patients undergoing treatment with coal tar and ultraviolet light. J Invest Dermatol 77:181–185Google Scholar
  23. WHO (1981) Health effects of combined exposures in the work environment. Technical Report Series 662Google Scholar
  24. Yamasaki E, Ames BN (1977) Concentration of mutagens from urine by adsorption with nonpolar resin XAD-2. Cigarette smokers have mutagenic urine. Proc Natl Acad Sci USA 74:3555–3559Google Scholar
  25. Regional Cancer Organisation (May 1980) Chemotherapy Instruction Manual, Cookridge Hospital, LeedsGoogle Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • R. P. Bos
    • 1
  • A. O. Leenaars
    • 1
  • J. L. G. Theuws
    • 1
  • P. Th. Henderson
    • 1
  1. 1.Institute of Pharmacology, Toxicology Section, University of NijmegenFaculty of MedicineNijmegenThe Netherlands

Personalised recommendations