title: Comparative genomic hybridization analysis of N-methyl-N'-nitrosoguanidine-induced rat gastrointestinal tumors discloses a cytogenetic fingerprint.
abstract: Exposure to N-nitroso compounds is thought to play a key role in the development of gastric cancer in humans. The alkylating agent N-methyl-N'-nitrosoguanidine (MNNG) is carcinogenic in a number of animal models and its preferential target tissue is the gastrointestinal (GI) tract. The genetic synteny among rats and humans makes the rat a useful model for induced tumorigenesis. However, because of the limited availability of genetic information, cytogenetic and molecular studies are rarely performed in the rat. We report an investigation of eight MNNG-induced rat gastric tumors by comparative genomic hybridization (CGH). The tumors were from forestomach (induced by a single dose of MNNG) and from pylorus (induced by chronic exposure). CGH identified a genetic fingerprint of chromosomal imbalances common to the two types of the tumors. Frequent gains were observed at 9q11-q12, 15q22-25, and Xq11-q12. Forestomach carcinomas were also characterized by gains in 7q11-q12, 20q13, and Yq12. Homology studies between the rat and human genomes indicate the presence of genes within these regions with potential relevance to tumorigenesis in the GI tract. Our findings provide new insights into the location of genes involved in MNNG-induced gastric cancer initiation and/or progression in the rat.
authors.affiliation: Centre for Molecular Genetics and Toxicology, University of Wales, Swansea, United Kingdom. corso_c@uclink.berkeley.edu
authors.forename: Chiara
authors.initials: C
authors.lastname: Corso
authors.forename: James M
authors.initials: JM
authors.lastname: Parry
mesh_terms: D000818:Animals; D002869:Chromosome Aberrations / Q000139:chemically induced; D016172:DNA Fingerprinting; D004273:DNA, Neoplasm / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008769:Methylnitronitrosoguanidine; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; D008769:Methylnitronitrosoguanidine