Effects of dietary selenium on hepatic and renal tumorigenesis induced in rats by diethylnitrosamine

Abstract

Seven groups of female Sprague-Dawley rats (approximately 200 gm initial body weight) were injected i.p. with a single subcarcinogenic dose of diethylnitrosamine (40 mg per kg body weight) between 8 to 10 hr after partial hepatectomy, and after a recovery period of 3 weeks (herein called induction stage) received 0.05% phenobarbital in the diet for the rest of the experiment (promotion stage). The rats were fed a 20% casein-based diet containing 0.16 ppm of selenium or the same diet supplemented with 4 or 6 ppm of selenium as sodium selenite. The effects of these three dietary regimens were tested when administered 9 to 11 days before and during induction, 1 week before and during promotion or during the entire experiment. Pair-feeding conditions were used to minimize influences due to differences in food intake and growth. Despite similarities in food intakes, the growth rates in groups receiving the 6 ppm-selenium diet during promotion or during the entire experiment were in general significantly lower than in rats fed the 4 ppm-selenium diet or the 0.16 ppm-selenium basal diet. Survival rates were also significantly reduced in rats fed the 4 and 6 ppm-selenium diets during promotion or during the entire experiment. In rats killed at the 19th week for interim assessment of the experiment's progress, the stereologically analyzed numerical and volumetric densities of hepatic premalignant hyperplastic nodules did not differ significantly between groups. All the remaining rats were killed at the 46th week.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of inorganic selenium compounds on oxidative DNA damage

“…Understanding this seemingly contradictory behavior may help explain conflicting results seen in anticancer studies using Na 2 SeO 3 [19,32,33,50,51]. We have clearly demonstrated the ability of inorganic selenium compounds both to prevent and generate DNA damage using a biologically-relevant DNA damage assay, but the complex behaviors of these compounds with regard to their concentration and concentration of H 2 O 2 in vivo merit further study.…”

“…In addition, a plethora of anticancer studies have been conducted with sodium selenite (Na 2 SeO 3 ), showing conflicting results [15][16][17]29,[31][32][33]. Few studies have been conducted with either sodium selenate (Na 2 SeO 4 ) and selenium dioxide (SeO 2 ).…”

Inhibition of aflatoxin B1-induced cell injury by selenium: an in vitro study

“…It has been shown in both in vivo and in vitro that AFB1, after metabolic activation by cytochrome P-450 enzymes, readily binds to DNA.3,4,5 The formation of aflatoxin-DNA adducts may cause mutations during DNA transcription and is considered a critical initiation step in cancer development.6 6 Selenium is an essential trace nutrient in the mammalian diet and deficiency of this element can cause a variety of severe pathological conditions .7 It has been reported that selenium can act as an anticarcinogen and inhibit the initiation and/or progression of certain chemical-and viral-induced tumours. 8,9,10 Studies in laboratory animals suggested that selenium was also effective in inhibiting aflatoxin-induced hepatocarcinogenesis. 11,12,13 3 However, the cellular mechanism of selenium as an anticarcinogen to aflatoxin has not been fully elucidated.…”

Lack of effects of selenium onN‐nitrosomethylbenzylamine‐induced tumorigenesis, DNA methylation, and oncogene expression in rats and mice

“…Lijinsky and co-workers (2) did not find any effects of selenium on nitrosomethylcyclohexylamine-induced esophageal cancer and nitrosomethylcarboxypropylamine-induced bladder cancer in rats. In contrast, Dorado and associates (3) reported that selenium can promote diethylnitrosamine-induced renal tumors in rats. No antitumor effects of selenium were reported in several other tumorigenesis experiments (4,5).…”