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), Journal Name: Proc. Soc. Exp. Biol. Med.; (United States) Vol. 175:2; ISSN PSEBA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
BODY
CARBON TETRACHLORIDE
CHLORINATED ALIPHATIC HYDROCARBONS
CHRONIC INTAKE
CORN OIL
DIGESTIVE SYSTEM
DNA
ESTERS
GLANDS
HALOGENATED ALIPHATIC HYDROCARBONS
INTAKE
LABELLED COMPOUNDS
LABELLING
LIPIDS
LIVER
MAMMALS
MEDICINE
MICE
NUCLEIC ACIDS
OILS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
OTHER ORGANIC COMPOUNDS
PATHOLOGICAL CHANGES
RODENTS
SURGERY
TRIGLYCERIDES
TRITIUM COMPOUNDS
VEGETABLE OILS
VERTEBRATES