Prevention of adverse effects of γ-ray irradiation after metallothionein induction by bismuth subnitrate in mice

doi:10.1016/0277-5379(89)90341-6

European Journal of Cancer and Clinical Oncology

Volume 25, Issue 12, December 1989, Pages 1727-1731

https://doi.org/10.1016/0277-5379(89)90341-6 Get rights and content

Abstract

The effect of preinduction of metallonthionein (MT) by bismuth subnitrate (BSN) on the adverse effects and antitumor activity of γ-ray irradiation was investigated in mice. Preinduction of MT by oral administration of BSN significantly reduced the lethal effects and bone marrow injury caused by total body irradiation with γ-rays. A significant increase in the MT concentration in bone marrow was observed in mice treated with BSN. In tumor-bearing mice, pretreatment with BSN did not compromise the antitumor activity of γ-ray irradiation although bone marrow injury was remarkably suppressed. These results suggest that BSN pretreatment is an effective method for protection against side-effects in radiotherapy.

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Cited by (51)

Bismuth
2015, Handbook on the Toxicology of Metals: Fourth Edition
Bismuth compounds are considered to be poorly to moderately absorbed after inhalation or ingestion, but there are no quantitative data. Absorbed bismuth is distributed throughout the soft tissues and bone, the highest concentrations being found in the kidney and liver. Absorbed bismuth is excreted primarily through the urine. The biological half-time for whole-body retention is about 5 days, but intranuclear inclusions containing bismuth seem to remain for years in the kidneys of patients treated with bismuth compounds.
High-level exposure causes renal failure associated with degeneration and necrosis of the epithelium of the renal proximal tubules, fatty changes and necrosis of the liver, reversible dysfunction of the nervous system, skin eruptions, and pigmentation of the gums and intestine.
There are no reports on occupational exposures. For the general population, the total daily intake in food is approximately 5-20 μg, with much smaller amounts contributed by air and water. An important source of exposure for specific segments of the population in the past was the therapeutic use of bismuth compounds. The cosmetic use of bismuth compounds continues to be fairly widespread. Bismuth subnitrate has been used to induce metallothionein in heart tissue and kidneys and to attenuate the toxicity of doxorubicin (Adriamycin) and cisplatin compounds, respectively.
Bismuth compounds have also been used in the production of nanomaterials and in treatments, especially for bacterial gastrointestinal infections. Radioisotopes of bismuth have been evaluated for radiotherapy of tumors.
Short reviews on the toxicology of bismuth have been published by Browning (1969), Filipova (1971), Arena (1974), Fowler and Vouk (1986), and Fowler and Sexton (2007).
Bismuth
2014, Handbook on the Toxicology of Metals
Bismuth compounds are considered to be poorly to moderately absorbed after inhalation or ingestion, but there are no quantitative data. Absorbed bismuth is distributed throughout the soft tissues and bone, the highest concentrations being found in the kidney and liver. Absorbed bismuth is excreted primarily through the urine. The biological half-time for whole-body retention is about 5 days, but intranuclear inclusions containing bismuth seem to remain for years in the kidneys of patients treated with bismuth compounds.
High-level exposure causes renal failure associated with degeneration and necrosis of the epithelium of the renal proximal tubules, fatty changes and necrosis of the liver, reversible dysfunction of the nervous system, skin eruptions, and pigmentation of the gums and intestine.
There are no reports on occupational exposures. For the general population, the total daily intake in food is approximately 5-20 μg, with much smaller amounts contributed by air and water. An important source of exposure for specific segments of the population in the past was the therapeutic use of bismuth compounds. The cosmetic use of bismuth compounds continues to be fairly widespread. Bismuth subnitrate has been used to induce metallothionein in heart tissue and kidneys and to attenuate the toxicity of doxorubicin (Adriamycin) and cisplatin compounds, respectively.
Bismuth compounds have also been used in the production of nanomaterials and in treatments, especially for bacterial gastrointestinal infections. Radioisotopes of bismuth have been evaluated for radiotherapy of tumors.
Short reviews on the toxicology of bismuth have been published by Browning (1969), Filipova (1971), Arena (1974), Fowler and Vouk (1986), and Fowler and Sexton (2007).
Bioaccumulation and lack of oxidative stress response in the ragworm H. diversicolor following exposure to <sup>226</sup>Ra in sediment
2009, Journal of Environmental Radioactivity
Citation Excerpt :
There were no obvious effects of any of the treatments on the capacity of the polychaetes to scavenge different oxyradicals. Earlier studies have shown that ionising radiation may cause oxidative stress in tissues (Thornally and Vasak, 1985; Satoh et al., 1989), but exposure levels have then been substantially higher than the activity used in the present study. Gamma and beta radiation has earlier been shown to affect aquatic organisms, e.g. the water flea Daphnia magna (Gilbin et al., 2008) and the polychaete Ophryotrocha (Knowles and Greenwood, 1997), but there is a paucity of studies on alpha-emitters such as 226Ra.
The main effluent from oil and gas production, produced water, from some platforms in the North Sea contains elevated concentrations of ²²⁶Ra. The aim of this study was to investigate whether ²²⁶Ra in sediment would accumulate in and affect sediment-dwelling organisms. In addition, we wanted to determine if the bioavailability would be modulated by the presence of a scale inhibitor which is used during oil and gas production. Hediste diversicolor was therefore exposed to different levels of ²²⁶Ra (30–6600 Bq kg⁻¹) in combination with scale inhibitor in the sediments in a flow through system. The levels of radioactivity in the exposures were close to levels that can be measured in proximity to oil/gas production facilities. ²²⁶Ra spiked to natural sediment partitioned into pore water and accumulated in the sediment-dwelling polychaete following a four-week exposure period. The results suggest that ²²⁶Ra did not bind strongly to sediment (low sediment:water partitioning coefficient), but it was not shown to bioaccumulate in any great extent (bioaccumulation factors of 0.019–0.022). Exposure of H. diversicolor in sediments with up to 6600 Bq kg⁻¹ ²²⁶Ra had no measurable effect on the total oxyradical scavenging capacity of the organisms compared to control. So although they accumulated the alpha-emitter, the treatments did not appear to cause oxidative stress in polychaete tissues.
Bismuth
2007, Handbook on the Toxicology of Metals, Third Edition
Metallothionein-I transgenic mice are not protected from γ-radiation
1999, Toxicology Letters
Metallothionein (MT) has been proposed to play a protective role against the toxic effects of free radicals and electrophiles, such as those produced by γ-radiation. Therefore, this study was designed to determine whether MT-transgenic mice, which carry 56 copies of the MT-I transgene and have higher tissue MT concentrations, are resistant to the toxic effects of γ-radiation. Mice were exposed to ¹³⁷cesium radiation, and survival was followed for 30 days. At all doses (7-12 Gy) examined, no difference in the survival was observed between control and MT-transgenic mice. The average survival times between control and MT-transgenic mice were also similar. Leukocytes were decreased 78±7% and 75±11% in control and MT-transgenic mice respectively 5 days after radiation. Furthermore, MT-transgenic mice were also equally susceptible as control mice to the lethal toxic effects produced by cyclophosphamide (1.75 mmol/kg, ip). In summary, MT-I transgenic mice are not protected against the toxic effects produced by γ-radiation or cyclophosphamide.
Metallothionein in radiation exposure: Its induction and protective role
1999, Toxicology
Since its discovery about 40 years ago, there has been a wide interdisciplinary research interest in metallothionein (MT) on its physiological and toxicological aspects. Functionally, MT is involved not only in metal detoxification and homeostasis, but also in scavenging free radicals during oxidative damage. Among over 4500 publications which can be retrieved by Medline search, only about 50 reports have been published on the relationship of MT with ionizing and UV radiation. In this review, we have evaluated critically the published data on the induced synthesis of MT by radiation, and the potential functions of MT in radiation induced cell damage. MT mRNA expression or MT synthesis was found to be induced by exposure of cells in vitro or tissues in vivo to ionizing or UV radiation. In most of the studies in animals and tissue cultures, high doses of ionizing radiation were used to induce MT, and, therefore, it is difficult to extrapolate these results to low level of repeated exposures to radiation in humans. Induced synthesis of MT is considered as one of the mechanisms involved in the adaptive response to low dose radiation exposure. The presence of MT in normal cells may provide protective effects from radiation-induced genotoxicity and cytotoxicity. However, in tumor cells, the presence of MT can result in drug and radiation resistance as well. These effects are modulated by other cellular factors, besides MT, such as antioxidants, and by the cell cycle stages in cell proliferation and differentiation.

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Prevention of adverse effects of γ-ray irradiation after metallothionein induction by bismuth subnitrate in mice

Abstract

Adv Radiat Biol

Environ Res

Toxicol Appl Pharmacol

Biochem Biophys Res Commun

Biochem Pharmacol

Anal Biochem

Toxicol Appl Pharmacol

J Biol Chem

Mortality of rhesus monkeys after single total body irradiation

Am J Roentgenol Radiat Ther

Pharmacological aspects of the vascular permeability changes in the rat's intestine following abdominal radiation

Br J Radiol

The mechanism of death following whole body radiation

Br J Radiol

Radioresistance in cells with high content of metallothionein

Experientia

A cadmium protein from equine kidney cortex

J Am Chem Soc