Alterations of the Dutt1/Robo1 gene in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats

Mol Carcinog. 2004 Aug;40(4):241-6. doi: 10.1002/mc.20037.

Abstract

Abnormalities of tumor suppressor genes (TSGs) on chromosome 3p are known to be important for the development of human lung cancers. In the present study, we investigated alterations of the Dutt1/Robo1 gene, as a possible tumor suppressor in this region, in rat lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP). 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 wk 25. A total of 12 lung adenocarcinomas were obtained and total RNAs were extracted from each for assessment of aberrant transcripts of the Dutt1/Robo1 gene by reverse transcription (RT)-polymerase chain reaction (PCR) analysis. Aberrant transcripts bearing deletions of nucleotides (nt) 55-4318, 89-4346, 605-4221, and 929-4318 were detected in four of 12 adenocarcinomas (33.3%). Loss or reduced expression of the Dutt1/Robo1 gene was not found in any of the adenocarcinomas. Genomic DNAs extracted from six adenocarcinomas for Southern blot analysis did not show any evidence of deletion or gross rearrangement of the Dutt1/Robo1 gene. These results suggest that alterations of the Dutt1/Robo1 gene may be involved in the development of some lung adenocarcinomas induced by BHP in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / chemically induced
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Southern
  • Carcinogens / pharmacology
  • Cell Transformation, Neoplastic / chemically induced
  • Cell Transformation, Neoplastic / genetics*
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Male
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Nitrosamines / pharmacology
  • Rats
  • Receptors, Immunologic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism

Substances

  • Carcinogens
  • Nerve Tissue Proteins
  • Nitrosamines
  • Receptors, Immunologic
  • Tumor Suppressor Proteins
  • roundabout protein
  • diisopropanolnitrosamine