Table 4.
Animal studies with radon.
| First Author Year of Publication | Species | Group Size | Type of Treatment and Dose | Time of Analysis after Exposure | Disease Model | Endpoints | Most Important Findings | Ref. |
|---|---|---|---|---|---|---|---|---|
| Takahashi et al., 2006 | Mice (SPF NC/Nga, female, 5 weeks) Mice (C57BL/6, male, 6 weeks) |
n= 4–9 | Drinking water; 203 Bq/L; approximate amount of radon ingested by each mouse 140–176, 68–85 and 0.86–1.08 Bq/kg week |
Up to 4 weeks | Atopic dermatitis model: sensitization with 5% purified picrylchloride Lung metastasis model: injection of B16 melanoma cells (both 2 weeks after start of radon treatment) |
Atopic dermatitis: Skin severity score, Plasma IgE Lung metastasis: number of metastasis |
Lower skin severity score and lower plasma IgE, only after radon pretreatment, Lower number of lung metastasis only after radon pretreatment and small number of inoculated tumor cells |
[132] |
| Kataoka et al., 2011 | Mice (BALB/c, male, 7–8 weeks, 25 g) |
n = 5 (Exp.3) n = 4–7 (Exp.4) n = 5–6 (Exp.5) |
Exp.3: inhalation for 24 h, 4000 Bq/m3 Exp:4 600 and 3500 Bq/m3 Exp.5: 180 Bq/m3 for 6 h |
Exp.3: directly Exp.4: 4 h Exp.5: 24 h |
Alcohol-induced oxidative damage; CCl4-induced hepathopathy | SOD activity Catalase activity ALD-activity and t-GSH in brain and liver |
Protective effect of radon on oxidative damage | [126] |
| Kataoka et al., 2011 | Mice (BALB/c, male, 7 weeks, 25 g) | n= 4–6 | Inhalation, 18 kBq/m3 for 6 h |
24 h | CCl4-induced hepatic and renal damage | t-GSH content, lipid peroxide levels, and GPx and GR activity in liver and kidney GOT, GPT, ALP activity, CRE, and T-CHO in serum |
Radon inhalation inhibits oxidative damage of liver and kidney | [125] |
| Kataoka et al., 2011 | Mice (BALB/c, male, 7 weeks, 25 g) | n = 5 | Inhalation, 250, 500, 1000, 2000, or 4000 Bq/m3 for 0.5, 1, 2, 4, or 8 days | Directly | Healthy | SOD activity in brain, lung, thymus, heart, liver, stomach, pancreas, kidney | Activation of SOD; in plasma, brain, and lung strong and rapid response (enhancement); in liver, heart, pancreas, and small intestine only after low and high concentrations; in thymus and kidney after low concentration; no change in stomach | [129] |
| Kataoka et al., 2012 | Mice (ICR, female, 8 weeks, 28 g) |
n = 5–8 | Inhalation, 1000 or 2000 Bq/m3 for 24 h or (L(+)-ascorbic acid injection or DL-α- tocopherol injection |
24 h | CCl4-induced hepathopathy | SOD activity, catalase activity, GPx activity, t-GSH, LP levels and TG in the liver; GOT, GPT activity, TG and T-CHO levels in the serum; and histological examination of liver tissue | Decreased activities of GOT and GPT in serum; decreased TG levels in liver significantly higher SOD, catalase and GPx activity in livers; radon inhalation has an antioxidative effect against CCl4-induced hepatopathy that is comparable to treatment with AA or α-tocopherol |
[127] |
| Kataoka et al., 2012 | Mice (ICR, female, 8 weeks, 28 g) |
n = 5–8 | Inhalation, 1000 or 2000 Bq/m3 for 24 h or DL-α-tocopherol injection different concentrations) | 24 h | CCl4-induced hepathopathy | SOD, catalase, t-GSH, and LP in kidneys CRE level in serum, | Decrease of CRE an LP levels; radon inhalation has an antioxidative effect comparable to the treatment with α-tocopherol at a dose of 300–500 mg/kg weight | [133] |
| Kataoka et al., 2012 | Mice (ICR, female, 8 weeks, 28 g) |
n = 6–7 | Inhalation, 2000 Bq/m3 for 24 h | 2 h | Carrageenan-induced inflammatory paw edema | SOD activity, catalase activity, t-GSH content, LP levels, TNF-α, NO, and paw histology. |
Paw volume significantly decreased; lower TNF- α and NO levels; SOD activity increased; fewer infiltrating leukocytes; increased SOD and catalase activities | [134] |
| Nishiyama et al., 2012 | Mice (BALB/c, male, 7 weeks, 23 g) |
n = 8 | Inhalation, 2000 Bq/m3 for 8 days | Directly | Dextran sulfate sodium (DSS) model of colitis (while radon exposure) | MPO, NO, TNF-α, SOD, CAT, t-GSH), LPO level, and Histology, DAI and weight gain | Significant lower DAI score; less shortened colon; lower plasma TNF- α and MPO activity in colon; enhanced SOD activity and tGSH content; lower LPO level in the colon and NO level in plasma | [135] |
| Toyota et al., 2012 | Mice (C57BL/6J, male, 8 weeks, 20 g) |
n = 4–6 | Inhalation, 4000 Bq/m3 for 24 h |
6 and 24 h | Acute alcohol-induced hepatopathy | SOD, catalase, t-GSH, GPx, GR, TG, and lipid peroxide in liver, GOT and GPT, activity and the TG, T-CHO in serum | Radon treatment activates antioxidative functions and inhibits acute alcohol-induced oxidative damage, hepatopathy and fatty liver in mice | [136] |
| Nishiyama et al., 2013 | Mice, (C57BL/6J, male, 9 weeks, 25–28 g) |
n = 5–8 | Inhalation, 1000, 2500, and 5500 Bq/m3 for 24 h | 4 days | Streptozotocin-induced Type-1 Diabetes (after radon exposure) | SOD activity, CAT activity, t-GSH content, LPO, blood glucose, serum insulin, and body weight | Higher SOD activity and t-GSH content, lower LPO levels; significantly suppressed blood glucose elevation and body weight decrease; higher serum insulin; radon inhalation partially suppressed type-1 diabetes induced by STZ administration | [137] |
| Yamato et al., 2013 | Mice (male ICR, 8 weeks, 38 g) |
n = 5–10 | Inhalation, 1000 or 2000 Bq/m3 for 24 h | Up to 35 min (licking response), no information for other endpoints | Formalin-induced transient inflammatory pain | licking response (pain), TNF-α, NO, paw histology, SOD and CAT activities, total glutathione (t-GSH) content, and LPO levels | Enhanced SOD-activity, t-GSH content in serum and paws, reduced number of leukocytes, reduced TNF-α and NO level | [138] |
| Etani et al., 2016 | Mice (male, 8 weeks, 32–38 g) |
n = 8–9 (drinking treatment) n = 6 (inhalation) |
Drinking water: 338 ± 11 Bq/L for 2 weeks Inhalation: 2000 Bq/m3 for 24 h |
3 h | PO model of hyperuricemia (induced after radon treatment) | Activities of XOD, SOD andCAT; levels of t-GSH and proteins in liver and kidney | Radon-inhalation activates antioxidative function and reduces serum uric acid levels | [139] |
| Kataoka et al., 2016 | Mice (ICR, male, 8 weeks; 33–40 g) |
n = 5–6 | Inhalation, 1000 Bq/m3 for 24 h and/or pregabalin treatment. | 30 min, 60 min, 90 min, 120 min | CCI—induced neuropathic pain | von Frey Test (pain), SOD activity, catalase activity, t-GSH content, and LP level in paw. | Pregabalin and radon has mitigative effect on pain after CCI due to antioxidative function after radon inhalation | [140] |
| Etani et al., 2017 |
Mice (BALB/c, male, 8 weeks, 25–28 g) |
n = 8 (drinking treatment) n = 8 (inhalation) |
Drinking water: 663 ± 36 Bq/L for 2 weeks Inhalation: 2000 Bq/m3 for 24 h |
1 h | Gastric mucosal injury induced by oral ethanol administration (induced after radon treatment) | UI and HI: SOD and CAT activity, and the levels of t-GSH in stomachs |
Lower UI and IHI after radon treatment; activation of antioxidative mechanisms | [141] |
| Kataoka et al., 2017 | Mice (BALB/c, male, 8 weeks, 24–28 g) | n = 7 | Inhalation, 500–2000 Bq/m3 for 24 h | Unclear | Healthy | NF-κB, NIK, IKK-β, ATM; total SOD, Mn-SOD and Cu/Zn-SOD activities and protein levels | Induction of SOD proteins, mainly Mn-SOD; Mn-SOD induced by NF-κB activation stimulated by DNA damage and oxidative stress | [130] |
| Pei et al., 2017 | Mice, (BALB/c, male, 15 g) | n = 6 | Inhalation, 100,000 Bq/m3, 12 h/d, for up to cumulative doses of 60 WLM |
Directly | Healthy | circRNA, H&E, Caspase 3 |
Enhanced Caspase 3 expression, circRNA profiles are changed | [142] |
| Paletta et al. 1975 | Rat (male, 200 g) |
n = 5 | Series 1: Rn 12.5 nCi/L, RaB/Rn 0,25; Series 2: Rn 110 nCi/L, RaB/Rn 0,33 Different doses to organs? |
12 d | Healthy | Corticosteroid level in serum | 2 maxima of corticosteroid after exposure, one after 8 h, one after 5 (low) or 9 h (high concentration) | [143] |
| Taya et al., 1994 | Rat (male, 4–6 months old) |
n = 10–25 | 120–990 WLM (dose rate 7–9 WLM/h; 725–770 Bq/m3) | 7–28 d | Healthy | Proliferation in epithelial cells of respiratory tract; binucleate alveolar macrophages (AM) and/or micronuclei | Labelling indices increased after exposure; highest in bronchial epithelial cells; binculeate AM as well as induction of micronuclei was increased after exposure; binucleate AM with micronuclei were only induced in exposed animals; no inflammation |
[144] |
| Ma et al., 1996 | Rats (Wistar, male, 30 weeks) |
n = 3 | Inhalation, 1000–5000 kBq/m3 or 400–1600 kBq/m3 for 4 or 16 h | Directly | Healthy | SOD activity in blood, kidney, spleen, and liver | Increase after 4 h, decrease after 16 h of exposure | [128] |
| Collier et al., 1997 | Rats (Sprague-Dawley, male, 2–12 month, | n = 2–6 | Inhalation, 200–1600 WLM, 250–7142 WL for 1–27.5 days | 14 d | Healthy | Cell number, nuclear abberations, number of macrophages and macrophage proliferation in lung lavage fluid, H&E and BrdU staining of lung sections | Positive dose-response for most effects | [145] |
| Cui et al., 2008 | Rats (Wistar) |
n = 6 | Inhalation; 60, 90, and 120 working level months (WLM) in total; inhalation for 8 h per day, 6 days per week | No information | Healthy | MNR, hprt assay in lymphocytes, and tracheal-bronchial epithelial cells | Dose-dependent increase of MNR, the mutation frequency of hprt is increased with accumulated dose, can be used as biomarkers for genetic changes after radon exposure | [146] |
| Yamaoka et al., 1993 | Rabbits | n = 10–14 | Inhalation of nebulized radon water; 7–10 kBq/L or 14–18 kBq/L | Directly and 2 h | Healthy | Lipid peroxide, SOD, membrane fluidity in brain, spleen, lung, liver and serum | Enhanced SOD activity, reduced lipid peroxide levels | [147] |
| Kataoka et al., 2014 | Mongolian gerbil MGS/sea, (female, 8 weeks, 50 g) | n = 5–7 | Inhalation, 2000 Bq/m3 for 24 h | Directly | Transient global cerebral ischemia induced by bilateral occlusion of the common carotid artery (3 days before radon treatment) |
Brain histology, SOD activity, CAT activity, and t-GSH content in the brain and serum. | Number of damaged neurons significantly lower; increased SOD activity; unchanged t-GSH | [148] |
Abbreviations: WT: wild type, PO: potassium oxonate, UI: ulcer index, IHI: index of histological injury, SOD: superoxide dismutase, XOD: xanthine oxidase, CAT: catalase, GPx: glutathione peroxidase, GR: glutathione reductase, GOT: glutamic oxaloacetic transaminase, GPT: glutamic pyruvic transaminase, ALP: alkaline phosphatase, CRE: creatinine, T-CHO: total cholesterol, LP: lipid peroxidase TG: triglyceride, AA: L(+)-ascorbic acid, TNF-α: tumor necrosis factor alpha, t-GSH: total glutathione content, NO: nitric monoxide, CCI: chronic constriction injury, NIK: NF-κB–inducing kinase, IKK-β: inhibitor of κB kinase-β, ATM: ataxia-telangiectasia mutated kinase, MPO: myeloperoxidase, DAI: disease activity index, WLM: working level months, hprt hypoxanthine phosphoribosyl transferase, MNR: micronuclei rate.