Effect of selenium on the induction of breast fibroadenomas by adenovirus type 9 and 1,2‐dimethylhydrazine‐induced bowel carcinogenesis in rats

Abstract

Selenium in its organic and inorganic forms has been shown to inhibit the development of chemically induced, spontaneous and transplanted tumors. The present investigation was performed to study the effect of selenium (4 micrograms per ml of drinking water) on tumorigenesis of adenovirus-type-9-induced breast fibroadenomas and on 1,2-dimethylhydrazine-induced bowel carcinogenesis in WF rats. It was found that identical treatment with Se under identical conditions and with no obvious toxic effects on the rats (1) resulted in inhibition of DMH-induced large-bowel carcinogenesis; (2) facilitated induction of small-bowel cancer by the same carcinogen in the same animals, and (3) greatly facilitated induction of breast fibroadenoma by adenovirus type 9 in the same strain of rats. The effect of Se treatment on DMH-induced large-bowel carcinogenesis confirms previous findings and proves that the opposite effect on fibroadenoma development is not due to differences in e.g. effective dose, animal strains or condition of the animals. It is not yet clear through which mechanisms Se exerts these effects.

Current Ideas on Selenium as a Chemopreventive Agent

“…It should be noted that a few reports have demonstrated that selenium supplementa tion has enhanced the appearance of tumors [6,16,27,28]. The original report on the carcinogenic potential of selenium examined rats fed seleniferous wheat and com [27], The rats developed a high incidence of liver DAB = 3-methyl-4-diaminoazobenzene; AAF = 2-acetylaminofluorine; DEN = diethylnitrosamine; AFBI = aflatoxin Bl; DMH = 1,2-dimethylhydrazine; MAM = methylazoxymethanol acetate; AOM = azoxymethane; BOP = bis(2-oxopropyl)nitrosamine; DMBA -7,12-dimethylbenzanthraccne; MNU = mcthylnitrosourea; Ad-9 = adenovirus type 9; MMTV = mouse mammary tumor virus; BP = benzo(a)pyrene; MNNG = N-methyl-N'-nitro-N-nitrosoguanidine; MBN = methylbenzylnitrosamine.…”

“…Subsequent experiments failed to re peat this observation and several authors have suggested that the diagnosis of dysplastic liver lesions did not adequately discrimi nate between cirrhotic changes and incipient neoplasms [3,4], A second study reported Adenovirus-9-enhanced fibroadenoma inci dence in the rat mammary gland [28]. Two recent studies in liver and skin have demon strated that under very specific experimental protocols for tumor induction, selenium can enhance the tumorigenic response [6,16].…”

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

“…An increasing body of evidence suggests that selenium can reduce the incidence or retard the development of experimental tumors in the liver and other organs of laboratory animals (1)(2)(3)(4)(5)(6)(7). Exceptions to this antineoplastic property have been also noted (8,9). We have recently reported (10) that 2 ppm of selenium (as sodium selenite) added to a Torula yeast-based diet did not affect the incidence of hepatic hyperplastic nodules and carcinomas induced in weanling Wistar male rats by diethylnitrosamine (DEN) as the initiator carcinogen and phenobarbital (PB) as the promoter, using the two-stage model of hepatocarcinogenesis developed by Peraino et al (11).…”

“…3.55 f 0.49(8) 47.05 f 12.86 0.66 f 0.02(14) 0.71 f 0.06(3)17.64 f 9.82 Mean f S.E. Number of animals in parentheses.…”