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No Mutations of Lysophosphatidic Acid Receptor Genes in Lung Adenocarcinomas Induced by N-Nitrosobis(2-hydroxypropyl)amine in Rats.

Abstract
Lysophosphatidic acid (LPA) is a bioactive phospholipid that stimulates cell proliferation and migration, and protects cells from apoptosis. It interacts with specific G protein-coupled transmembrane receptors. Recently, frequent mutations of the LPA receptor-1 (LPA1) gene were detected in rat lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP). In this study, to evaluate the involvement of other LPA receptor gene alterations during lung carcinogenesis, we investigated mutations of the LPA2, LPA3, LPA4 and LPA5 genes in lung adenocarcinomas induced by BHP in rats. Fifteen male Wistar rats, 6 weeks of age, were given 2000 ppm BHP in their drinking water for 12 weeks and then maintained without further treatment until sacrifice at 25 weeks, and 15 adenocarcinomas were obtained. Genomic DNAs were extracted from frozen tissues, and the LPA2, LPA3, LPA4 and LPA5 genes were examined for mutations, using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. No mutations of LPA2, LPA3, LPA4 and LPA5 were detected in the 15 adenocarcinomas. These results suggest that alterations due to LPA2, LPA3, LPA4 and LPA5 gene mutations might not be involved in the development of lung adenocarcinomas induced by BHP in rats.
AuthorsNaoko Wakabayashi, Megumu Tsujino, Masaki Tajiri, Midori Taki, Ayumi Koshino, Hiroko Ikeda, Nobuyuki Fukushima, Toshifumi Tsujiuchi
JournalJournal of toxicologic pathology (J Toxicol Pathol) Vol. 23 Issue 1 Pg. 63-6 (Mar 2010) ISSN: 1881-915X [Electronic] Japan
PMID22272013 (Publication Type: Journal Article)

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