1,2-Dimethylhydrazine-induced premalignant alterations in the S-adenosylmethionine/S-adenosylhomocysteine ratio and membrane lipid lateral diffusion of the rat distal colon.
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.
Department of Medicine, University of Chicago, IL.
A G
AG
Halline
P K
PK
Dudeja
T A
TA
Brasitus
D019813:1,2-Dimethylhydrazine; D000818:Animals; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D003652:Decanoic Acids / Q000378:metabolism; D004058:Diffusion; D004127:Dimethylhydrazines / Q000633:toxicity*; D006710:Homocysteine / Q000031:analogs & derivatives*; D008563:Membrane Lipids / Q000378:metabolism*; D008716:Methionine Adenosyltransferase / Q000378:metabolism; D008763:Methylhydrazines / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D012435:S-Adenosylhomocysteine / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism*
D003652:Decanoic Acids; D004127:Dimethylhydrazines; D008563:Membrane Lipids; D008763:Methylhydrazines; D006710:Homocysteine; C021247:pyrenedecanoic acid; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008716:Methionine Adenosyltransferase; D019813:1,2-Dimethylhydrazine