EVALUATION OF TRANSGENIC MOUSE BIOASSAYS FOR IDENTIFYING CARCINOGENS AND NONCARCINOGENS

Data supporting the use of transgenic lines to identify carcinogens an d noncarcinogens are thus far based on a limited number of chemicals f or which there are also long-term bioassay results in rats and/or mice . Six chemicals have been tested in the heterozygous p53-deficient mic e and 13 in the Tg . AC line. The results show that the p53(def) respo nds rapidly to mutagenic carcinogens and the Tg . AC responds rapidly to both mutagenic and nonmutagenic carcinogens. Neither transgenic lin e responded to the noncarcinogens that were tested. The p53(def) line failed to respond to two nonmutagenic carcinogens (N-methyloacrylamide and reserpine), the Tg . AC line failed to respond to ethyl acrylate, a nonmutagenic chemical that induced tumors of the forestomach when a dministered by gavage, and to triethanolamine that caused an increase in hepatocellular tumors in B6C3F1 mice via skin painting. Both of the latter chemicals are examples of highly specific responses related to either route of administration or to strain susceptibility. Further e fforts to evaluate the range of chemicals to which these transgenic li nes respond are currently in progress.