Alterations in the Fhit gene in pancreatic duct adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamsters

Mol Carcinog. 2003 Feb;36(2):60-6. doi: 10.1002/mc.10099.

Abstract

Alteration of the Fhit gene was investigated in pancreatic duct adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine (BOP) in Syrian golden hamsters. The animals received 70 mg/kg BOP, followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with DL-ethionine and then L-methionine and administration of 20 mg/kg BOP. A total of 15 pancreatic duct adenocarcinomas were obtained 10 wk after the beginning of the experiment, and total RNAs were extracted from each for assessment of aberrant transcription of the Fhit gene by reverse transcription-polymerase chain reaction analysis. Aberrant transcripts lacking nucleotides in the regions of nt -75 to 348, nt -15 to 348, or nt -75 to 178 were detected in 11 adenocarcinomas (73.3%). Southern blot analysis of eight tumors did not show any evidence of gross rearrangement or deletion. These results indicated that changes in the Fhit gene occurred frequently and thus may have played a role in the development of pancreatic duct adenocarcinomas induced by BOP in hamsters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Anhydride Hydrolases*
  • Adenocarcinoma / chemically induced*
  • Adenocarcinoma / genetics*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carcinoma, Pancreatic Ductal / chemically induced*
  • Carcinoma, Pancreatic Ductal / genetics*
  • Cricetinae
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mesocricetus
  • Molecular Sequence Data
  • Mutation / drug effects
  • Mutation / genetics*
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics*
  • Nitrosamines / pharmacology*
  • Pancreas / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid

Substances

  • Neoplasm Proteins
  • Nitrosamines
  • RNA, Messenger
  • fragile histidine triad protein
  • nitrosobis(2-oxopropyl)amine
  • Acid Anhydride Hydrolases