Tumor spectrum in the p53 heterozygous zeta globin-promoted Tg.AC (v-Ha-ras) bitransgenic mouse model.
The use of a bitransgenic mouse model for cancer is an effective approach for studying the impact of specific carcinogens and the occurrence of tissue-specific lesions. We studied the novel p53 heterozygous zeta globin-promoted Tg.AC (v-Ha-ras) mouse model because these mice contain a carcinogen-inducible ras oncogene and one functional p53 tumor suppressor allele, both of which occur frequently in human cancers. Our aim was to characterize the short-term control and chemically induced tumor spectrum in this novel model. Mice were placed on basal semipurified diet containing 20% soy protein for 2 weeks prior to random allocation to groups. Subsequently, 15 male and 15 female mice were administered corn oil vehicle alone or containing benzo(a)pyrene (20 mg/kg body weight) via oral gavage 2 times per week for 10 weeks with subsequent observation for 18 weeks. Mice exhibited lesions characteristic of FVB/N, p53 heterozygous and Tg.AC mouse models. However, an array of unique, novel lesions were observed including uterine leiomyosarcomas, mammary gland carcinomas, mammary squamous cell carcinomas, and parotid salivary gland carcinomas suggesting tissue-specific interactions of the 2 genotypes. Thus, this bitransgenic model may provide further insight into the mechanistic interaction of 2 genes commonly mutated in neoplasia.
Martin
Keith R
KR
Laboratory of Environmental Carcinogenesis & Mutagenesis, NIEHS, Research Triangle Park, North Carolina, USA. krm12@psu.edu
Jokinen
Michael P
MP
Honeycutt
Hayden P
HP
Quinn
Anita
A
Kari
Frank W
FW
Barrett
J Carl
JC
French
John E
JE
D000483:Alleles; D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity*; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D004334:Drug Administration Schedule / Q000662:veterinary; D005260:Female; D020868:Gene Silencing; D016158:Genes, p53; D011905:Genes, ras; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced* / Q000145:classification / Q000235:genetics* / Q000473:pathology / Q000662:veterinary
D002273:Carcinogens; D001564:Benzo(a)pyrene; D005914:Globins