In vitro binding of mirex by mouse hepatocytes
Mirex (dodecachlorooctahydro-1,3,4-metheno-2H-cyclobuta(cd)+ ++pentalene) is a hepatic tumorigen that is shown to cause marked disturbances in hepatic cell ploidy in rodents. Kinetic measurements of (/sup 14/C)mirex binding were performed in freshly prepared diploid (DP) and polyploid (PP) hepatocytes, as well as in erythrocytes, under controlled conditions. The binding of mirex to hepatocytes, irrespective of their ploidy, was partially Na+-dependent and totally Ca2+-independent. Variations in temperature and pH appeared to significantly inhibit mirex binding; the optimum binding was seen at 37 degrees C under physiological pH. The saturation kinetic data revealed that PP cells were saturated at a very low concentration of mirex (two- to threefold) compared to DP, exhibiting a high-affinity binding of mirex to PP with a low Km (347 nM) and Vmax (102 nmol/mg X min). The Km (550 nM) and Vmax (340 nmol/mg X min) values determined for DP cells were of higher magnitude, like those of erythrocytes (Km, 819 nM; Vmax, 330 nmol/mg X min), indicating that distinct differences exist in the binding affinities of three cell types. However, erythrocytes and DP cells showed close similarity in their Vmax values. Interestingly, mirex levels in the lipid compartments of DP and PP cells revealed no apparent differences. The results are discussed in terms of the possible susceptibility of PP cells and their role in the initiation of toxic response leading to hepatotumorigenesis in rodents.
- Research Organization:
- Union Univ., Albany, NY
- OSTI ID:
- 5809275
- Journal Information:
- J. Toxicol. Environ. Health; (United States), Journal Name: J. Toxicol. Environ. Health; (United States) Vol. 4; ISSN JTEHD
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ALKALI METALS
ALKALINE EARTH METALS
ANIMAL CELLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CALCIUM
CARBON 14 COMPOUNDS
ELEMENTS
ERYTHROCYTES
IN VITRO
INSECTICIDES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIVER CELLS
MAMMALS
MATERIALS
METALS
MICE
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
PESTICIDES
PH VALUE
REACTION KINETICS
RODENTS
SODIUM
SOMATIC CELLS
TEMPERATURE DEPENDENCE
TRACER TECHNIQUES
VERTEBRATES