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Journal Article 
Induction of hepatomas in mice by repeated oral administration of chloroform, with observations on sex differences 
Eschenbrenner, AB; Miller, E 
Journal of the National Cancer Institute
ISSN: 0027-8874
EISSN: 1460-2105 
Repeated feeding of carbon tetrachloride in olive-oil solution in amounts sufficient. to produce liver necrosis will induce hepatomas in mice (1-4). Chloroform produces central necrosis of the liver lobule, followed by regeneration of parenchymal cells in a manner similar to that produced with carbon tetrachloride and when given repeatedly will also induce hepatomas. In this report, experimental conditions leading to the induction of hepatomas with chloroform are given in detail while only a brief description of the tumors is given ince they appear to be indistinguishable from those induced with carbon tetrachloride. In a previous report ( 4), it was suggested that the cycles of repeated necrosis and repair in the liver might be an important factor in the induction of tumors with carbon tetrachloride. All reports (1-4), however, dealt only with the use of necrotizing doses. The use of a graded series of necrotizing and nonnecrotizing doses of chloroform has revealed an apparent necessity for the production of repeated liver necrosis in the induction of these tumors.