Responses of transgenic mouse lines p53(+/-) and Tg.AC to agents tested in conventional carcinogenicity bioassays.
The haplo-insufficient p53 knockout (p53+/-) and zetaglobin v-Ha-ras (Tg.AC) transgenic mouse models were compared to the conventional two rodent species carcinogen bioassay by prospectively testing nine chemicals. Seven of the chemicals classified as carcinogens in the conventional bioassay induced tumors in the liver or kidneys of B6C3F1 mice, and one (pentachlorophenol) also induced tumors in other tissues. Only three chemicals, furfuryl alcohol, pyridine, and pentachlorophenol, induced tumors in rats. The tumorigenic effect of pyridine was seen in F344 rats but not in Wistar strain rats. None of the chemicals induced tumors in the p53+/- transgenic mice, which is consistent with the absence of genotoxicity of these chemicals. Only two of the seven nongenotoxic carcinogens were positive in the Tg.AC model (lauric acid diethanolamine and pentachlorophenol). These results show that these transgenic models do not respond to many chemicals that show strain- or species-specific responses in conventional bioassays.
Spalding
J W
JW
National Institute of Environmental Health Sciences, Laboratory of Environmental Carcinogenesis and Mutagenesis, Research Triangle Park, North Carolina 27709, USA. spalding@niehs.nih.gov
French
J E
JE
Stasiewicz
S
S
Furedi-Machacek
M
M
Conner
F
F
Tice
R R
RR
Tennant
R W
RW
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D011905:Genes, ras; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics*
D002273:Carcinogens; D016159:Tumor Suppressor Protein p53