Thyroid tumours in rats and hepatomas in mice after griseofulvin treatment

Abstract

Summary.-Griseofulvin, an antibiotic used to treat dermatophytosis, was tested for carcinogenicity in mice, rats and hamsters. Three groups of mice and rats were given the drug in powdered diet in alternating 5-week periods for life, at dose levels of 3.000, 1-500 and 0-300 (mice) and 2.0%, 1-0% and 0-2% (rats). A group of mice and 3 groups of hamsters received continuous daily treatment for life with griseofulvin at 3-000, 1.5%, 0.300 and 0.1% dose levels respectively. A significant incidence of hepatic tumours was observed at the 2 higher treatment levels in mice. Also, statistically significant rates (P < 0.001 and/or P < 0.020) of thyroid tumours, indicating a dose-response, were recorded in male rats at the 2.00/ 1-0%0, and 0 2% dose levels, and in females at the 2.0°, and 1.0% dose levels. Hamsters did not develop neoplasms in response to treatment at any level.

Veterinary pharmacovigilance. Part 6. Predictability of adverse reactions in animals from laboratory toxicology studies

“…The mechanism is unclear since it does not disrupt microtubules like some other spindle poisons but it does appear to bind to tubulin or at least to microtubule-associated proteins (Grisham et al, 1973;Wehland et al, 1977;Ueno, 1985;De Carli & Larizza, 1988). Moreover, studies in mice demonstrated that griseofulvin was hepatocarcinogenic in mice after oral dosing and it resulted in thyroid tumours in rats (Rustia & Shubik, 1978). Dietary administration to mice resulted in hepatotoxicity, disruption of hepatic architecture and lesions which had the appearance of liver tumours (De Matteis et al, 1966).…”

“…Moreover, studies in mice demonstrated that griseofulvin was hepatocarcinogenic in mice after oral dosing and it resulted in thyroid tumours in rats (Rustia & Shubik, 1978). Dietary administration to mice resulted in hepatotoxicity, disruption of hepatic architecture and lesions which had the appearance of liver tumours (De Matteis et al.…”

Effects of griseofulvin in medium‐term liver carcinogenesis assay and peripheral blood micronucleus test in rat

“…In mice, the prolonged oral administration of GF disturbs hepatic porphyrin metabolism, and induces liver damage and increased hepatic tumor incidence [5][6][7][8]. In another study long-term feeding of GF (0.2% to 2% in the diet) led to thyroid adenomas and carcinomas, but the limited studies available do not indicate definitely whether the compound is a hepatocarcinogen in this species [9]. Barich et al [10] showed that GF promoted skin tumor development in mice when given orally after methylcholanthrene initiation, but no published studies on the tumor promoting potential of GF in the liver are available.…”

Induction of Hepatocellular Carcinomas in the Egyptian Toad <i>Bufo regularis</i> by an Antifungal Drug (Griseofulvin)

“…Induction o f hepatomas by G F was also reported after administration o f milligram quantities to infant mice [11]. Dietary ex posure to G F produced a significant incidence o f hepa tocellular tumors in mice, thyroid tumors in rats, but no carcinogenic activity in hamsters [12]. G F may also act either as a promoting or a carcinogenic agent, depending on the circumstances o f its administration [4], A cocarcinogenic effect on skin tumor development in mice was noted when G F was administered orally before, during or after topical treatment with methylcholanthrene [13][14][15].…”