1,2-Dimethylhydrazine-induced premalignant alterations in the S-adenosylmethionine/S-adenosylhomocysteine ratio and membrane lipid lateral diffusion of the rat distal colon

Biochim Biophys Acta. 1988 Sep 15;944(1):101-7. doi: 10.1016/0005-2736(88)90322-7.

Abstract

Prior studies by our laboratory, utilizing the 1,2-dimethylhydrazine experimental model of colonic cancer, had shown that administration of this procarcinogen for 5 weeks was found to increase phospholipid methyltransferase activity and the fluidity of rat distal colonic brush-border membranes. The present studies were conducted to further explore these 'premalignant' colonic phenomena. Male albino rats of the Sherman strain were subcutaneously injected with dimethylhydrazine (20 mg/kg body weight per week) or diluent for 5 weeks. Animals from each group were killed, distal colonic tissue harvested and the levels of S-adenosylmethionine, S-adenosylhomocysteine and decarboxylated S-adenosylmethionine measured by high performance liquid chromatography. The activity of methionine adenosyltransferase was also examined in these tissues. Additionally, brush-border membranes were isolated from the distal colonocytes of control and treated-animals and examined and compared with respect to their phospholipid methylation activities as well as their lipid fluidity as assessed by the rotational mobilities of the probes 1,6-diphenyl-1,3,5-hexatriene and DL-12-(9-anthroyl)stearic acid and translational mobility of the fluorophore pyrenedecanoic acid. The results of these studies demonstrated: (1) phospholipid methyltransferase activity in rat colonic plasma membranes was increased concomitantly with increases in the cellular levels of S-adenosylmethionine and the S-adenosylmethionine/S-adenosylhomocysteine ratio in the distal colonic segment of treated-animals; and (2) the lateral diffusion of rat distal colonic brush-border membrane lipids, as assessed by the ratio of excimer/monomer fluorescence intensities of the fluorophore pyrenedecanoate, was also increased after dimethylhydrazine administration to these animals for 5 weeks.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1,2-Dimethylhydrazine
  • Animals
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / metabolism*
  • Decanoic Acids / metabolism
  • Diffusion
  • Dimethylhydrazines / toxicity*
  • Homocysteine / analogs & derivatives*
  • Membrane Lipids / metabolism*
  • Methionine Adenosyltransferase / metabolism
  • Methylhydrazines / toxicity*
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / metabolism*
  • Rats
  • S-Adenosylhomocysteine / metabolism*
  • S-Adenosylmethionine / metabolism*

Substances

  • Decanoic Acids
  • Dimethylhydrazines
  • Membrane Lipids
  • Methylhydrazines
  • Homocysteine
  • pyrenedecanoic acid
  • S-Adenosylmethionine
  • S-Adenosylhomocysteine
  • Methionine Adenosyltransferase
  • 1,2-Dimethylhydrazine