Aneuploid nuclear DNA content in some enzyme-altered rat liver foci during tumor promotion
Most rat hepatomas are aneuploid. To determine if ploidy changes can be detected also during hepatocarcinogenesis, male F344 rats were partially hepatectomized; 18 hrs later they were given 50 mg/kg weight diethylnitrosamine i.p. and fed a promoting choline-deficient diet containing 0.05% phenobarbital. Controls received partial hepatectomy, i.p. saline, and choline-supplemented diet. Rats were sacrificed at various times and liver sections were stained with a combined Feulgen-..gamma..-glutamyl transferase stain. DNA content of hepatocytes in enzyme-altered foci (EAF) thus identified was measured by microspectrophotometry. No EAF were found in control animals. Nuclear DNA values of control hepatocytes had a trimodal distribution, with peaks corresponding to 2N, 4N, and 8N ploidy. A similar pattern was seen in most EAF from treated rats. However, at each treatment time a minority of EAF (23, 14, and 36% at 10, 16 and 29 wks, respectively) evinced an aneuploid pattern. Out of a total of 59 EAF counted in 10 rats, 15 were aneuploid. Although aneuploidy is essential in the progression stage of cancer, this finding indicates it is already present during promotion, long before hepatomas can be diagnosed. More important, it demonstrates that EAF heterogeneity is not only phenotypic but also genomic. Aneuploid DNA content in some EAF may be a marker for abnormal cell populations from which carcinomas are most likely to arise.
- Research Organization:
- Case Western Reserve Univ., Cleveland, OH
- OSTI ID:
- 5970811
- Journal Information:
- Biochemical Genetics: Gene Structure and Function II; (United States), Journal Name: Biochemical Genetics: Gene Structure and Function II; (United States)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HEPATOMAS
ANEUPLOIDY
LIVER
CHEMICAL ANALYSIS
NITROSAMINES
TOXICITY
CARCINOGENESIS
DIET
DNA
RATS
SPECTROPHOTOMETRY
AMINES
ANIMALS
BODY
DIGESTIVE SYSTEM
DISEASES
GLANDS
MAMMALS
NEOPLASMS
NITROSO COMPOUNDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
PLOIDY
RODENTS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)