Three transgenic mouse lines carrying v-Ha-ras (TG-SH), c-myc (TG-M) or c-neu (TG-NK) oncogenes under regulatory control of mouse mammary tumor virus (MMTV) long terminal repeat (LTR) sequences were evaluated for responses to two chemical
carcinogens.
p-Cresidine, a mutagenic urinary bladder
carcinogen, increased the incidence of urinary bladder
carcinomas in males and females in all three lines, and these
tumors occurred at comparable incidences and grade in transgenic and non-transgenic mice.
p-Cresidine did not affect the rates of mammary or
salivary gland neoplasms in transgenic mice; these
tumors did not occur in non-transgenic littermates. No other
tumor types were observed in exposed or control animals.
Reserpine, a non-mutagenic mammary gland
carcinogen, was administered under the same protocol, but the high control rates of mammary gland
adenocarcinomas in the TG-M and TG-NK strains made it difficult to detect any
tumor-enhancing effect of
reserpine. However, the incidences of multiple mammary gland
tumors were significantly increased in dosed females from both lines. The incidence of mammary gland
adenocarcinomas was significantly increased in TG-SH females receiving 5 p.p.m.
reserpine.
Reserpine did not induce any carcinogenic effects in non-transgenic mice. These results indicate that the transcriptional regulation of these three transgenes is a major determinant in the response to
p-cresidine and
reserpine. The use of transgenic models for the general detection of
carcinogens may require lines in which appropriate genes are targeted for expression in many tissues, or lines in which critical genes have been inactivated.