1,2-Dimethylhydrazine-induced alterations in Na+-H+ exchange in rat colonic brush-border membrane vesicles.
1,2-Dimethylhydrazine, in weekly subcutaneous (s.c.) doses of 20 mg/kg body weight, produces colonic tumors in virtually 100% of rodents, with a latency period of approximately 6 months. To determine whether alterations in Na+-H+ exchange existed before the development of dimethylhydrazine-induced colon cancer, rats were given s.c. injections of this agent (20 mg/kg body wt. per per week) or diluent for 5 weeks. Animals were then killed, rat colonic brush-border membrane vesicles prepared and amiloride-sensitive sodium-stimulated proton efflux was measured and compared in control and treated-preparations. The results of these studies demonstrated that dimethylhydrazine treatment: (1) significantly increased the Vmax of this exchange without altering the Km for sodium of this exchange process, utilizing the fluorescent pH-sensitive dye, acridine orange; 22Na flux experiments also demonstrated an increase in amiloride-sensitive proton-stimulated sodium influx across treated-membrane vesicles; (2) did not appear to significantly influence Na+ permeability or proton conductance in treated-preparations compared to their control counterparts; and (3) did not significantly affect the kinetic parameters of amiloride-sensitive sodium-stimulated proton efflux in renal cortex brush-border membrane vesicles using acridine orange. This data, therefore, suggests that alterations in Na+-H+ exchange in rat colonic brush-border membranes may be involved in the malignant transformation process induced by this procarcinogen in the large intestine.
Brasitus
T A
TA
Department of Medicine, University of Chicago Hospitals & Clinics, IL 60637.
Dudeja
P K
PK
Foster
E S
ES
D019813:1,2-Dimethylhydrazine; D000165:Acridine Orange; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004127:Dimethylhydrazines / Q000494:pharmacology*; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D007672:Kidney Cortex / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008763:Methylhydrazines / Q000494:pharmacology*; D008871:Microvilli / Q000378:metabolism; D011522:Protons; D051381:Rats; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology; D012979:Sodium Radioisotopes; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D004127:Dimethylhydrazines; D005456:Fluorescent Dyes; D008763:Methylhydrazines; D011522:Protons; D012979:Sodium Radioisotopes; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D012964:Sodium; D000165:Acridine Orange; D019813:1,2-Dimethylhydrazine