Induction of retrovirus gene expression by selenium compounds

doi:10.1016/0165-1218(83)90154-4

Mutation Research/Genetic Toxicology

Volume 117, Issues 1–2, April 1983, Pages 67-78

https://doi.org/10.1016/0165-1218(83)90154-4 Get rights and content

Abstract

Sodium selenite, sodium selenate, selenium oxide, selenophypoxanthine, selenopurine, selenocysteine, selenoethionine and selenomethionine were tested for their ability to induce endogenous retrovirus expression in cultured AKR mouse embryo fibroblasts. All except selenoethionine were highly toxic to the cells. Only selenomethionine however, had the ability to induce virus expression under the conditions used. The level of virus induction (plaque-forming-units/10⁵ cells) was roughly proportional to dose over the range of concentrations from 0.25 mM to 5.0 mM. Induction was best observed when a treatment duration of 48 h was used and required the treatment of actively dividing cells. The induction and the cytotoxic effects of selenomethionine could be abrogated by simultaneous treatment with methionine. A ratio of methionine to selenomethionine of 1:10 inhibited induction by approx. 60% while equivalent amounts of methionine inhibited selenomethionine-mediated induction by greater than 96%, indicating that methionine was more efficiently recognized by the cells than was selenomethionine. A possible mechanism for selenomethionine induction involving the production of undermethylated DNA is presented.

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Determination of selenoethionine by flow injection-hydride generation-atomic absorption spectrometry/high-performance liquid chromatography-hydride generation-high power nitrogen microwave-induced plasma mass spectrometry
2001, Analytica Chimica Acta
Citation Excerpt :
Selenoethionine (ethyl(3-amino-3-carboxy-1-propyl)selenide), a dialkyl selenide (C2H5–Se–CH2–CH2–CH(NH2)COOH), will carry a positive charge at relatively low pH (localized to be protonated amino group), but will be zwitterionic (amino group, carboxylate group) at intermediate pH, and become anionic (carboxylate group) at higher pH [2]. The Seet has been tested for the ability to induce endogenous retrovirus expression in cultured AKR mouse embryo fibroblasts [3] and found to be less toxic to the cells compared to the selenomethionine (Semet) and other amino acids [3]. The production of 1-methyladenine (1-MeAde) by gonad-stimulated substance (GSS) has also inhibited by Seet, a competitive inhibitors of methionine [4].
A simple direct flow injection hydride generation atomic absorption spectrometric method was developed using sodium tetrahydroborate and hydrochloric acid for the determination of selenoethonine (Seet) that excluded any chemical pretreatment prior to hydride generation. The detection limit (3σ of blank) of the method was 0.25 ng ml⁻¹ selenium (standard solutions in Milli-Q water). The reproducibility (R.S.D. of three analyses performed on three different days) and the repeatability (R.S.D. of seven successive analyses) of the method were 9.2% for 5.05 ng ml⁻¹ and 2.8–9.5% for 20.0–1.00 ng ml⁻¹ of standard selenium (Milli-Q water), respectively. The calibration graph was linear up to 20.0 ng ml⁻¹. This HG method is very promising and was successfully applied for the on-line estimation of Seet (spiked) in human urine with using high-performance liquid chromatography-hydride generation-high power nitrogen microwave-induced plasma mass spectrometry (HPLC-HG-N₂-MIP-MS). The separation was performed on a GS-220 gel-permeating column with a 25 mM tetramethylammonium hydroxide+25 mM malonic acid buffer (pH 7.5), which showed 26–30% signal suppression due to less volatile hydride formation from Seet among the mobile phases examined. The recovery of Seet that was prepared in the above mobile phase is about 74% as that of the Seet prepared in Milli-Q water. In the PRP-X100 anion-exchange column with the 15 mM phosphate (pH 7.0) mobile phase, Seet eluted out after 600 s keeping a broad peak with enlarging the baseline signal. The concentration of selenite found in the human urine was 3.6±0.2 μg l⁻¹ and that agreed well with the high-performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS) value (3.8±0.2 μg l⁻¹).
Analytical techniques applied to the speciation of selenium in environmental matrices
1994, Analytica Chimica Acta
The toxicity and essential nature of Se in the environment depend on its concentration and the chemical forms in which it is present. Se and its derivatives may be widely dispersed throughout the environment as a result of anthropogenic inputs such as fossil fuel combustion and industrial, agricultural and natural processes. In order to evaluate the effects of the different Se species on living organisms, sensitive analytical methods are required for their determination in complex environmental matrices. An overview is given of the importance of Se speciation and the distribution, accumulation and transformation of the species in the environment. The state of the art of various techniques is discussed. The main sources of errors in each step involved in the analytical methods are reported and the importance of quality control and the need to use reference materials are also stressed.
Embryotoxicity and dose-response relationships of selenium in hamsters
1990, Reproductive Toxicology
Pregnant hamsters were treated with selenite, selenate, and selenomethionine during the critical stages of embryogenesis. The dosing regimens were oral, intravenous, and osmotic minipump infusion. Malformations, mainly encephaloceles, were noted with oral and intravenous selenite and selenate but were associated with maternal toxicity manifested by inanition and weight loss. Fetal body weights and lengths were reduced in a dose-dependent manner with the inorganic forms. Single oral doses of selenomethionine above 77 μmol/kg induced similar malformations but not when the dose was delivered orally over four days nor by minipump over several days. Fetal body weights and lengths were decreased by selenomethionine in a dose-dependent manner. Maternal toxicity was pronounced with the higher doses of selenomethionine. Assigning a specific teratogenic effect to selenium is confounded by maternal toxicit.
Effects of cytidine analogs on methylation of DNA and retrovirus induction
1988, Mutation Research Letters
Several cytidine analogs with known mutagenic capability were tested for their effects on DNA methylation and on induction of endogenous murine retrovirus. For each of the compounds tested it was found that DNA methylation was inhibited at the same concentrations that were required to induce virus expression. With each compound it was observed that increased dose levels produced an increase in the ability to inhibit methylation and an increase in the ability to induce virus.
The genotoxicity of selenium
1985, Mutation Research/Reviews in Genetic Toxicology
Selenium at nutritional levels has been shown to have numerous anticarcinogenic or preventative effects against carcinogen-induced breast, colon, liver and skin cancer in animals. Many of these anticarcinogenic effects have been summarized. In addition, numerous mutagenic and antimutagenic effects of selenium compounds have been reported. Some of the selenium compounds frequently tested for mutagenicity are listed in Table 1. Because of the numerous reported anticarcinogenic and preventative effects of selenium, many individuals are supplementing their diets with amounts of selenium that are greater than the recommended daily requirement. Selenium is also used widely in industrial products such as selenium rectifiers, photoelectric batteries, alloys and paints. Because selenium at higher levels is known to be toxic, there should be a greater understanding about its genotoxic as well as its beneficial effect. The object of this review is to summarize experimental evidence both for the antimutagenic and the mutagenic effect of selenium.
Induction of retrovirus gene expression by aflatoxin B<inf>1</inf> and 2-acetylaminofluorene
1983, Mutation Research Letters
The abilities of 2-acetylaminofluorence (AAF) and aflatoxin B₁ (AFB) to induce the expression of endogenous murine retrovirus in AKR mouse embryo fibroblasts were examined. AFB was able to induce virus expression at concentrations as low as 0.067 μM, although the induction efficiency was increased at higher doses. AAF gave somewhat more variable results. In some experiments induction was observed with as little as 0.1 μM while in other experiments induction was not observed at concentrations as high as 100 μM. Addition of an S9 metabolizing system enhanced the ability of AAF to induce virus expression but also increased the background induction frequency. These results are discussed in relation to the mechanism of virus induction and the potential usefulness of virus induction as an assay for carcinogenic potential.

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Induction of retrovirus gene expression by selenium compounds

Abstract

Virology

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Mutation Res.

Mutation Res.

Virology

Virology

Virology

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Cancer Lett.

Cell

Virology

Mutation Res.