Alterations of the M6p/Igf2 receptor gene in lung adenocarcinomas induced by N‐nitrosobis(2‐hydroxypropyl)amine in rats

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Abstract
Alterations of the mannose 6‐phosphate/insulin‐like growth factor II receptor (M6p/lgf2r) gene were investigated in lung adenocarcinomas induced by N‐nitrosobis(2‐hydroxypropyl)amine (BHP) in rats. Male Wistar rats, 6 wk old, were given 2000 ppm BHP in their drinking water for 12 wk and maintained without further treatment until killed at week 25. A total of 12 lung adenocarcinomas were obtained, and total RNAs were extracted from each for assessment of mutations and levels of aberrant transcripts of the M6p/Igf2r gene by reverse transcription (RT)–polymerase chain reaction (PCR) single‐strand conformation polymorphism analysis and RT‐PCR analysis, respectively. No mutations were found in exons 27, 28, 31, 33, and 34. Aberrant transcripts bearing deletions of nt 3698 to 4902, 3366 to 4902, and 3817 to 4697 were detected in three of 12 adenocarcinomas (25%). These results suggest that alterations of the M6p/Igf2r gene may be involved in the development of lung adenocarcinomas induced by BHP in rats.