Induction of malignant transformation and mutagenesis in cell cultures by cancer chemotherapeutic agents

The bioassay of the rapidly growing list of chemicals that are now being added to the human environment by in vivo carcinogenesis studies is an insurmountable task. It is, therefore, hoped that the short‐term in vitro tests will be of predictive value in terms of human risk as prescreening methods. The oncogenic and mutagenic activity of cancer chemotherapeutic agents in such cell culture tests will be discussed: It has been one of the intriguing results of cancer research that active antineoplastic agents have been found to be carcinogenic. Various methods to investigate malignant transformation in cell culture by chemicals that have been developed are briefly introduced. Most presently used antitumor agents have been shown to be active in transforming mammalian cells. In general, the correlation between in vivo tumorigenicity and the in vitro results is satisfactory; a more recent example of this is the results obtained with the anthracyline antibiotics, Daunomycin and Adriamycin, and some of their derivatives. Since chemical mutagenesis and oncogenesis, although not necessarily causally related, appear to be well correlated, various mutagenesis assays have been introduced to prescreen our environment for hazardous chemicals, mutagens and carcinogens. The mutagenic activity of cancer chemotherapeutic agents in cell culture (bacteria, yeast, mammalian cells) will be briefly reviewed; studies with the anthracycline antibiotics and with 5‐azacytidine and the new antitumor agent, Pseudoisocytidine, will be emphasized. From the still very limited studies available, results on malignant transformation and mutagenesis in vitro correlate well with in vivo tumorigenicity data. Most, if not all, antineoplastic agents appear to possess oncogenic potential. It must be emphasized, however, that the in vitro short‐term tests still require further development and verification of their predictive value.