Risk Estimation for Leukemogenic Drugs
A number of drugs used in cancer chemotherapy are known to be highly leukemogenic. Because the cancer risks per unit dose can be estimated more precisely for these drugs than for many other human carcinogens, they provide a unique opportunity to test the predictions of cancer risk models, and bioassay outcomes. The available data on leukemia incidence following cytostatic drug treatment are reviewed, with regard to differences in potency. Quantitative data from animal bioassays are also used as the basis for potency estimates, and the correlation with the human data is examined. Chemical and biochemical properties of several of the drugs are then discussed, with view to explaining some of the observed differences in leukemogenic potency.
KeywordsPolycythemia Vera Carcinogenic Risk Cytostatic Drug Nitrogen Mustard Human Carcinogen
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- BEIR, 1980, “The Effects on Populations of Exposure to Low Levels of Ionizing Radiation”, Committee on the Biological Effects of Ionizing Radiation (BEIR I II ), National Academy of Sciences, Washington, D.C.Google Scholar
- Berk, P. D., Goldberg, J. D., Silverstein, M. N., Weinfeld, A., Donovan, P. B., Ellis, J. T., Landaw, S. A., Laszlo, J., Najean, Y., Pisciotta, A. V., and Wasserman, L. R., 1981, Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. New Engl. J. Med.. 304: 441.PubMedCrossRefGoogle Scholar
- Connors, T. A., 1987, Antitumor alkylating agents: cytotoxic actin and organ toxicity, in: Carcinogenicity of alkylating cytostatic drugs, (IARC Scientific Publications No 78), D. Schmähl, and J. M. Kaldor, eds., International Agency for Research on Cancer, Lyon.Google Scholar
- Gold, L. S., Sawyer, C. B., Magaw, R., Backman, G. M., de Veciana, M., Levinson, R., Hooper, N. K., Havender, W. R., Bernstein, L., Peto, R., Pike, M.C., and Ames, B. N., 1984, A carcinogenic potency database of the standardized results of animal bioassay. Environ Health Perspect., 58: 9.PubMedCrossRefGoogle Scholar
- Hemminki, K., Kallama, S., and Falck, K., 1983, Correlations of alkylating activity and mutagenicity in bacteria of cytostatic drugs, Acta Pharmacol. Toxicol., 53: 421.Google Scholar
- Hemminki, K., and Kallama, S., 1986, Reactions on nitrogen mustards with DNA, in: “Carcinogenicty of Alkylating Cytostatic Drugs (IARC Scientific Publications No 78)”, D. Schmähl, and J. M. Kaldor, eds, International Agency for Research on Cancer, LyonGoogle Scholar
- IARC, 1986, “Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Vol. 38, Tobacco smoking”, International Agency for Research on Cancer, LyonGoogle Scholar
- IARC, 1988, “Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Supplement No 7, Overall evaluations of carcinogenicity: An update of IARC Monographs Volumes 1–42”, International Agency for Research on Cancer, Lyon.Google Scholar
- Margison, G. P., and O’Connor, P. J., 1979, Nucleic acid modification by N-nitroso compounds, in: “Chemical carcinogens and DNA, Vol. I”, P. L. Grover, ed., CRC Press, Boca Raton, FloridaGoogle Scholar
- Pedersen-Bjergaard, J., Nissen, N. I., Sorensen, H. M., Hou-Jensen, K., Larson, M. S., Ernst, P., Ersbml, J., Knudtzon, S., and Rose, C., 1982, Acute non-lymphocytic leukemia in patients with ovarian carcinoma following long-term treatment with treosulfan (dihydroxybusulfan). Cancer, 45: 19.CrossRefGoogle Scholar
- Penn, I., 1987, Malignancies induced by drugs therapy: a review, in: Carcinogenicity of alkylating cytostatic drugs, (IARC Scientific Publications No 78), D. Schmähl, and J. M. Kaldor, eds., International Agency for Research on Cancer, Lyon.Google Scholar