Liver nuclear DNA synthesis in mice following carbon tetrachloride administration or partial hepatectomy
Long-term, continuous (twice per week) administration of CCl/sub 4/ to male mice resulted in a high incidence of liver nodules which appear to be resistant to the necrotizing effects of CCl/sub 4/ but showed no features of malignant neoplasia. Liver nuclear DNA synthesis was compared in mice given CCl/sub 4/ and in mice subjected to partial hepatectomy (PH). Mice were given by gavage corn oil or CCl/sub 4/ in corn oil for periods of 2 to 25 weeks and several mice were subjected to PH after 12 and 25 weeks of corn oil treatment. Mice were given (/sup 3/H)TdR during liver regeneration and newly synthesized liver nuclear DNA was isolated and separated by BND-cellulose chromatography. Greater than 85% of the labeled DNA from PH mice eluted from BND-cellulose columns as double-stranded (ds) DNA with single-stranded (ss) regions or ends and less than 15% as ds DNA. When mice were treated with CCl/sub 4/ for 8 weeks or longer a significantly greater portion of liver nuclear DNA eluted as ds DNA. Administration of HU and 5-FU with (/sup 3/H)TdR decreased (/sup 3/H)TdR incorporation into DNA to low levels incompatible with unscheduled DNA synthesis. Single doses of CCl/sub 4/ given to mice treated with corn oil for 2 to 12 weeks provided newly synthesized DNA which was primarily (>80%) ds DNA with ss regions or ends, but after 25 weeks of corn oil administration, a single dose of CCl/sub 4/ resulted in newly synthesized DNA with a greater proportion of ds DNA. The high labeling of ds DNA in mice treated with CCl/sub 4/ may have resulted from an alternate pathway of DNA synthesis catalyzed by the enzymes or enzyme complexes associated with semiconservative DNA synthesis or from proliferation of nonparenchymal cells with a rapid turn-over rate.
- Research Organization:
- Univ. of Vermont, Burlington
- OSTI ID:
- 6903266
- Journal Information:
- Proc. Soc. Exp. Biol. Med.; (United States), Vol. 175:2
- Country of Publication:
- United States
- Language:
- English
Similar Records
Effect of chlordecone on carbon tetrachloride-induced increase in calcium uptake in isolated perfused rat liver
Effects of acetaminophen on cadmium metabolism in mice
Related Subjects
CARBON TETRACHLORIDE
BIOLOGICAL EFFECTS
CHRONIC INTAKE
DNA
BIOLOGICAL PATHWAYS
LABELLING
LIVER
PATHOLOGICAL CHANGES
CORN OIL
MICE
SURGERY
TRITIUM COMPOUNDS
ANIMALS
BODY
CHLORINATED ALIPHATIC HYDROCARBONS
DIGESTIVE SYSTEM
ESTERS
GLANDS
HALOGENATED ALIPHATIC HYDROCARBONS
INTAKE
LABELLED COMPOUNDS
LIPIDS
MAMMALS
MEDICINE
NUCLEIC ACIDS
OILS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
OTHER ORGANIC COMPOUNDS
RODENTS
TRIGLYCERIDES
VEGETABLE OILS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)