Induction of Renal Cell Tumors in Rats and Mice, and Enhancement of Hepatocellular Tumor Development in Mice after Long‐term Hydroquinone Treatment

Abstract

Hydroquinone (HQ) was administered to F344 rats and B6C3F1 mice of both sexes at a level of 0.8% in the diet for two years. This treatment induced renal tubular hyperplasia as well as adenomas, predominantly in males of both species, and was associated with chronic nephropathy in rats. In addition, the occurrence of epithelial hyperplasia of the renal papilla was increased in male rats. Foci of cellular alteration of the liver were significantly reduced in number by HQ in rats, but in contrast, were increased in mice, where development of hepatocellular adenoma was also enhanced in males. The incidence of squamous cell hyperplasia of the forestomach epithelium was significantly higher in mice of both sexes given HQ than in the controls, but no corresponding increase in tumor development was observed. The present study strongly indicates potential renal carcinogenicity of HQ in male rats and hepatocarcinogenicity in male mice. Thus, it is possible that HQ, which is present in the human environment, may play a role in cancer development in man.

Differences in the Nephrotoxicity of Hydroquinone Among Fischer 344 and Sprague-Dawley Rats and B6c3f1 Mice

“…Renal tubular hyperplasia and renal tubular adenomas were seen in low-dose (25 mg/kg) and high-dose (50 mg/kg) male rats, with none occurring in the controls. Shibata et al (1991) have confirmed the male F344 rat findings in more recent studies in which HQ was administered in the diet at 0.8% for 2 yr. The higher dose level used by Shibata et al (351 mg/kg/d based on average feed consum ption) resulted in a proportionately greater incidence of renal adenomas in male rats (47% incidence vs. 15% incidence in NTP study).…”

Inhibitory effects of phenolic compounds on development of naturally occurring preneoplastic hepatocytic foci in long-term feeding studies using male F344 rats

“…Hydroquinone is known to cause increased incidences of preneoplastic foci and hepatocellular adenomas in B6C3F1 mice, but not in F344 rats, after 2-year administration [4,22]. In addition, the phenolic antioxidant butylated hydroxyanisole acts as a liver tumor promoter in initiation/promotion protocols using male B6C3F1 mice [23] and female SD rats [24].…”

Effect of Methimazole on Rat Renal Carcinogenesis Induced by N-Ethyl-N-Hydroxyethylnitrosamine

“…(3,4). Another renal tumor promoter, HQ, has been reported to enhance the development of nephropathies, notably tubular hyperplasias and adenomas, in male rats in chronic 2-yr bioassays (6,13). These chemicals appear to have different characteristics ; NTA is a weak carcinogen in its own right when given at high doses over long periods of time (8).…”

“…Methimazole, a thionamide with antioxidant properties, was recently reported to protect the rat kidney from cephaloridine-induced damage (13 Individual whole body and kidney weights were recorded at necropsy. The kidneys and samples of small intestine from BrdU-treated rats were fixed in 70% ethanol for 24 hr and processed using the avidin-biotin peroxidase complex (ABC) technique for immunohistochemical studies of cell proliferation and DNA synthesis (9).…”