Carcinogenic Effects of Immunosuppressive Drugs in Man

Abstract

There is hardly any other field in chemical carcinogenesis in which such good agreement between experimental and clinical results has been reached as in carcinogenesis induced by antineoplastic agents. As early as 1967, the carcinogenic effects of the two alkylating drugs cyclophosphamide and triazichone in rats were reported (Schmähl 1967). The results were systematically supported in later experiments and extended to other antineoplastic compounds (Schmähl and Osswald 1970). The investigations revealed that predominantly those antineoplastic drugs which have an alkylating mechanism of action had to be classified as potential carcinogens, whereas antimetabolites and antimitotics exerted practically no carcinogenic effects. The doses required to induce cancer in rats and mice corresponded to doses administered to patients on a mg/kg basis. The findings obtained in 1970 were later on confirmed in numerous investigations carried out in other laboratories (see review in Schmähl and Kaldor 1986). Experiments on the mechanism of the carcinogenic action of alkylating agents yielded the clear result that this type of carcinogenesis is not linked to the immunosuppressive porperties of alkylating agents, but is due to direct interaction between the alkylating agent and DNA.