PMID: 9537649Apr 16, 1998Paper

Role of tumor suppressor genes in transplacental lung carcinogenesis

Molecular Carcinogenesis
L A RollinsM S Miller

Abstract

Most human cancers involve multiple genetic changes, including activation of oncogenes such as Ki-ras-2 (Kras2) and inactivation of any one of a number of tumor suppressor genes such as p53 and members of the retinoblastoma (Rb) regulatory axis. As part of an ongoing project to determine how in utero exposure to chemical carcinogens affects the molecular pathogenesis of murine lung tumors, the p53 and p16Cdkn2a genes were analyzed by using paraffin-embedded lung tissues from mice treated transplacentally with 3-methylcholanthrene. Single-strand conformation polymorphism analysis of exons 5-8 of the p53 gene, as well as their flanking introns, demonstrated an absence of mutations at this gene locus. However, a genetic polymorphism was identified at nt 708 in intron 4 of the DBA/2 strain of mice 5 bp downstream of a 3' branching-point splice signal. Analysis of exons 1 and 2 of the Cdkn2a gene by single-strand conformation polymorphism and sequence analyses revealed mutations in exon 2 in 7% of the tumors examined. Tumor 23-1 exhibited a CAC-->TAC transition at nt 301 (His74-->Tyr74), and tumor 36-1 exhibited a GGG-->GAG transition at nucleotide 350 (Gly90-->Glu90). Northern blot analysis of 14 of the larger tumors showed a marke...Continue Reading

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Citations

Jan 15, 2000·Mutation Research·M HollsteinP Hainaut
Mar 25, 2014·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Sr Prem D'SouzaPrashantha Naik
Jul 11, 1998·Experimental Lung Research·M S MillerM G O'Sullivan
Jul 9, 2004·Toxicology and Applied Pharmacology·Mark Steven Miller
Jul 9, 2008·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Erling Dahl BorkamoOystein Fluge
Feb 17, 2006·Molecular Carcinogenesis·Heather S FloydMark Steven Miller

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