The autoradiographic identification of unscheduled DNA synthesis (UDS) in primary cultures of adult rat hepatocytes (HPC) has been proposed as a predictive test for mutagens/carcinogens. To assess the predictive value of this test, results in the hepatocyte UDS assay were compared with data for bacterial mutagenicity using a modified Ames test. Over 200 compounds representing a variety of chemical classes consisting of procarcinogens, ultimate carcinogens, and noncarcinogens were tested in each system. The accurate discrimination of many carcinogens/noncarcinogens was demonstrated by both systems. The induction of UDS in hepatocytes showed an excellent correlation with bacterial mutagenesis in response to polycyclic aromatic hydrocarbons, aromatic amines, biphenyls, nitrosamines, carbamates, azo-compounds, acridines, halogenated compounds, nitrosureas, quinolines, pyridines, purines, pyrimidines, esters and carbamates. Nitrocompounds, although active in bacteria, were poor inducers of UDS. The results support the complementary and confirmatory nature of these tests for genotoxic chemicals and indicate the usefulness of the hepatocyte UDS system as a component in a battery of short-term predictive tests for mutagens/carcinogens.

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A group of 45 monosubstituted aniline compounds was tested for the induction of point mutations in Salmonella typhimurium and Escherichia coli as well as for unscheduled DNA synthesis (UDS) in rat hepatocyte culture. Eleven compounds were bacterial mutagens, and five compounds induced UDS. Among these a correspondence between mutagenicity and UDS occurred for only two compounds (o-phenylenediamine and 4-aminobiphenyl), and these were also reported to be carcinogenic in rodents. Bacterial mutation was observed for one compound (p-phenylenediamine) not carcinogenic in rodents, and six suspect carcinogens were not detected in either test. In addition, eight compounds of unknown carcinogenic potential induced either bacterial mutation or UDS.

DNA damage induced by five ultimate carcinogens and five procarcinogens was evaluated by three methods: (1) DNA strand breaks in Crandall feline kidney (CRFK) cells measured by alkaline sucrose gradient centrifugation; (2) unscheduled DNA synthesis (UDS) in CRFK, Syrian hamster embryo (SHE), and rat hepatocyte cultures measured by liquid scintillation counting; and (3) UDS in CRFK, SHE, and rat hepatocyte cultures measured by autoradiography. DNA strand breaks were observed with three procarcinogens and four ultimate carcinogens. Only two procarcinogens and two ultimate carcinogens could be identified by liquid scintillation counting. A positive autoradiographic response for UDS was observed in CRFK cells with four of five ultimate carcinogens and one procarcinogen. SHE cells showed a positive autoradiographic response for UDS with all ultimate carcinogens and three procarcinogens. The autoradiographic system with primary rat hepatocyte cultures was the only one in which a positive response for DNA damage was elicited for all 10 carcinogens.