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The Effect of Prolonged Administration of Griseofulvin in Mice with Reference to Sex Differences¹

Department of Medicine, University of Minnesota Hospital, Minneapolis, Minnesota, and The Institute for Cancer Research (A.J.D.), Philadelphia, Pennsylvania

The effect of prolonged administration of griseofulvin (1% in the diet) to mice of both sexes has been studied, using the antibiotic in 3 different particle sizes. Levels of liver prophyrins were related to weight of livers and incidence and size of tumors. The intracellular localization of porphyrins was studied in frozen sections of tissue by fluorescence microscopy and in situ microfluorospectral analysis. The effect of withdrawal of the drug after 1 year of treatment was also investigated.

Increased liver size and elevated hepatic protoporphyrin were regular findings in the treated mice; significant alteration of the hepatic structure was also observed with the appearance of hepatomata in the most severe cases.

Liver enlargement, structural changes, and porphyria were all found to be more pronounced in male animals and a more marked reaction was noted after feeding fine particle size griseofulvin.

No significant change in either liver structure or levels of liver protoporphyrin was noted over a 4-month period following withdrawal of the drug.

¹ Aided by grants from the USPHS and the McNeil Laboratories.

² Present address: Toxicology Research Unit, Medical Research Council, Woodmansterne Road, Carshalton, Surrey, England.

Received 2/15/65. Revised 10/11/65.