Table 1.

Main cytogenetic and “omics” biomonitoring studies focused on the effect of radon on various biomarkers including microRNAs.

Study	Study Type	Study Type Methods	Total Size Samples	Location Detail of Exposure	Endpoint	Results
Wu et al., 2019 [10]	In vitro	qRT-PCR, flow cytometry, western blot analysis	Human bronchial epithelial BEAS-2B cell culture	Bronchial epithelial BEAS2B cells underwent exposure to radon for 30 min for 1, 5, 10, 15 and 20 days (Rn1, Rn5, Rn10, Rn15, Rn20).	miR-34a expression, apoptosis	miR-34a upregulation. PARP-1 and Bcl-2 downregulation and Bax upregulation in Rn20 cells.
Cui et al., 2013 [16]	In vitro	RNA isolation, microRNA microarray	Human bronchial BEAS2B cell line were cultured in LHC-8 medium	BEAS-2B cells were exposed to radon for 10, 20, 30 min at a concentration of 20,000 Bq/m3 during fifth passage for 1 (Rn5-1) and 20 generations (Rn5-20)	Modification of miRNA profile expression	163 miRNA upregulated and 155 miRNA downregulated in Rn-5-1 cells. 30 miRNA upregulated and 28 miRNA downregulated in Rn-5-20 cells
Meenakashi et al., 2017 [29]	In vivo	Micronucleus assay	25 healthy smokers and 25 healthy non-smokers (males)	Blood samples were exposed to radon gas with doses ranging between 0.3–12.6 mGy	Nucleoplasmic bridges as a biomarker of early DNA damage induced by radon	Radon exposure increased DNA damage in smokers compared to non-smokers
Zölzer et al., 2013 [36]	In vivo	Modified micronucleus-centromere test	84 uranium miners and 52 control persons	Mine workers exposed to 35–90 mSv	Micronuclei in blood lymphocytes	Uranium-exposed subjects had higher micronuclei frequency than non-exposed
Rosenberger et al., 2019 [53]	In vivo	Infinium OncoArray-500K	15,077 cases (lung cancer) and 13,522 controls, including 463 former uranium miners (61 cases:402 controls)	49 of 15 077 (0.3%) LC cases and 259 of 13 522 cancer-free controls (1.9%) had been occupationally exposed by a high cumulative dose exposure to radon and its progeny (WLM > 50)	occupational radon exposure was categorized into ≤50 (“unexposed”) and >50 WLM (“exposed”) as a threshold for significant elevated relative lung cancer risk	Genes belonging to the Gene Ontology term “DNA dealkylation involved in DNA repair” (GO:0006307; p = 0.0139) or the gene family HGNC:476 “microRNAs” (p = 0.0159) were enriched with LD-blockwise significance
Bulgakova et al., 2019 [57]	In vivo	DNA isolation, PCR-RFLP	44 radon-induced lung cancer patients and 41 lung cancer patients without high level of radon exposure and 42 age/sex-matched healthy controls	The average equivalent equilibrium radon volume activity (EEVA) for radon-induced lung cancer patients was 307.6 Bq/m3. The EEVA in the lung cancer patients living on the territory with a low level of radon were 40.6 Bq/m3	Polymorphism TP53 Arg72Pro (rs1042522) was showed a significantly higher risk of radon-induced lung cancer	Arg/Pro and Pro/Pro variants conferred an odds ratio (OR) of 6.95 (95 % confidence interval (CI) 2.41–20.05) and 1.45 (95 %CI 0.46–4.64), respectively. Individuals with Arg/Pro variant of TP53 gene exposed to high level of radon have a high risk of lung cancer (OR = 8.6; 95% CI 2.6–28.59) compared with people living in areas with a low level of radon
de Vocht et al., 2019 [90]	In vivo	Illumina Infinium HumanMethylation450 BeadChip	14,541 pregnant women with expected delivery dates between April 1991 and December 1992, which resulted in 14,062 live births of which 13,988 children were alive at 1 year of age	Estimates of potential radon exposure were based on long-term radon measurements from 479,000 homes across Great Britain and provided with a spatial resolution of 75-metre buffers as the percentage of dwellings exceeding the 200 Bq/m3. Radon Action Level in 6 classes: 1 (0–1%), 2 (1–3%), 3 (>3–5%), 4 (>5–10%), 5 (>10–30%) and 6 (>30–100%).	Once each residential address had a radon potential exposure class assigned, time spent at each address was calculated. This was merged with ARIES sample prevision dates, allowing time-weighted average potential radon exposures to be calculated up to the “mothers at middle age”, “children at 7” and “children at 15/17” sample extraction time points.	Average potential exposure to radon was associated in an exposure-dependent manner with methylation at cg25422346 in mothers during pregnancy, with no associations at middle age. For children, radon potential exposure was associated in an exposure-dependent manner with methylation of cg16451995 at birth, cg01864468 at age 7, and cg04912984, cg16105117, cg23988964, cg04945076, cg08601898, cg16260355 and cg26056703 in adolescence.
Chen et al., 2015 [93]	In vitro	qRT-PCR, western blot	Human bronchial epithelial (HBE) cells	Each time 1 × 106 HBE cells were seeded on transwell membrane and exposed to radon at the concentration of 20,000 Bq/m3 for 20 min. The exposure was repeated for 5 times (HR-5) or 10 times (HR-10)	let-7 microRNA and K-ras may be of potential markers in early diagnosis and therapy of radon-induced lung cancer	Down-regulation of let-7 and up-regulation of K-ras were revealed both in mRNA and in protein level in lung tissue of rats and HBE cells exposed to radon

HBE (Human Bronchial epithelial) cells; EEVA (Equivalent equilibrium radon volume activity); OR (Odds Ratio); WLM (Working Level Month); BEAS (Human bronchial epithelial).