Despite the fact that animal and human epidemiological studies confirmed a link between radon exposure in homes and increased risk of lung cancer in general population, other types of cancers induced by radon, such as leukemia, have not been consistently demonstrated. The aim of this review was to summarize data published thus far from ecological and case-control studies in exposed populations, taking into account radon dose estimation and evidence of radon-induced genotoxicity, in an effort to clarify the correlation between home radon exposure and incidence of childhood leukemia. Among 12 ecological studies, 11 reported a positive association between radon levels and elevated frequency of childhood leukemia, with 8 being significant. In conjunction with ecological studies, several case-control studies on indoor radon exposure and childhood leukemia were examined, and most investigations indicated a weak association with only a few showing significance. A major source of uncertainty in radon risk assessment is radon dose estimate. Methods for radon exposure measurement in homes of children are one of the factors that affect the risk estimates in a case-control study. The effects of radon-induced genetic damage were studied both in vitro and in vivo using genetic endpoints including chromosomal aberration (CA), micronuclei (MN) formation, gene mutation, and deletions and insertions. By applying a meta-analysis, an increased risk of childhood leukemia induced by indoor radon exposure was noted for overall leukemia and for acute lymphoblastic leukemia (ALL). Data thus indicated an association between environmental radon exposure and elevated leukemia incidence, but more evidence is required in both human investigations and animal mechanistic research before this assumption may be confirmed with certainty.

Cerium oxide nanoparticles (CeO2 NPs) have potential application for use in biomedical and in various consumer products. However, it is largely unclear whether CeO2 NPs have effects on male reproductive function. In this study, male mice were examined for toxicity, if any, following chronic oral administration of CeO2 NPs for 32 days. In each animal, epididymides were examined for sperm motility and DNA integrity. Bloods were tested for testosterone levels. Testicular tissues were collected to determine the element Ce content, the daily sperm production (DSP), marker enzymes such as ACP, G6PD, γ-GT and SDH, mRNA expression levels of steroidogenesis genes Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as steroidogenic factor-1 (SF-1) gene/protein levels. The results showed that CeO2 NPs (20 mg/kg and 40 mg/kg) increased the element Ce content in testis, the testis histopathological patterns and sperm DNA damage whereas decreased the testis weight, DSP and sperm motility. There were also remarkable reduction in testosterone levels and marker enzymes activities, down-regulated mRNA expression levels of several steroidogenesis genes such as Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as altered gene and protein expressions of SF-1. These results reveal the male reproductive toxicity of chronic exposure of CeO2 NPs in mice, hinting that the utilization of CeO2 NPs need to be carefully evaluated about their potential reproductive toxicity on the human health.

Reactive oxygen species (ROS) induced by exogenous toxicants are suggested to be involved in carcinogenesis by oxidative modification of DNA. 8-Hydroxyl-2-deoxyguanosine (8-OHdG) has been considered as a reliable biomarker for oxidative DNA damage both in vivo and in vitro studies. But the effect of smoking on oxidative damage has not yet been fully elucidated.

Background: Transforming growth factor β induced (TGFBI) product, an extracellular matrix (ECM) protein, has been implicated as a putative tumor suppressor in recent studies. Our previous findings revealed that expression of TGFBI gene is down-regulated in a variety of cancer cell lines and clinical tissue samples. In this study, ectopic expression of TGFBI was used to ascertain its role as a tumor suppressor and to determine the underlying mechanism of mesothelioma and breast cancer. Methods: Cells were stably transfected with pRc/CMV2-TGFBI and pRc/CMV2-empty vector with Lipofectamine Plus. Ectopic expression of TGFBI was quantified by using quantitative PCR and Western-blotting. Characterization of cell viability was assessed using growth curve, clonogenic survival and soft agar growth. The potential of tumor formation was evaluated by an in vivo mouse model. Cell cycle was analyzed via flow cytometry. Expressions of p21, p53, p16 and p14 were examined using Western-blotting. Senescent cells were sorted by using a Senescence β-Galactosidase Staining Kit. Telomerase activity was measured using quantitative telomerase detection kit. Results: In this study, an ectopic expression of TGFBI in two types of cancer cell lines, a mesothelioma cell line NCI-H28 and a breast cancer cell line MDA-MB-231 was found to have reduced the cellular growth, plating efficiency, and anchorage-independent growth. The tumorigenicity of these cancer cell lines as determined by subcutaneous inoculation in nude mice was similarly suppressed by TGFBI expression. Likewise, TGFBI expression reduced the proportion of S-phase while increased the proportion of G1 phase in these cells. The redistribution of cell cycle phase after re-expression of TGFBI was correspondent with transiently elevated expression of p21 and p53. The activities of senescence-associated β-galactosidase and telomerase were enhanced in TGFBI-transfected cells. Conclusion: Collectively, these results imply that TGFBI plays a suppressive role in the development of mesothelioma and breast cancer cells, possibly through inhibitions of cell proliferation, delaying of G1-S phase transition, and induction of senescence.

Due to widely commercial applications of silver nanoparticles (Ag NPs), toxicity assessment of this NP is of great importance. This study aimed to investigate the oxidative stress and heat shock response of Ag NPs at different doses to A549 and HepG2 cells. After treatment with different concentrations of Ag NPs for 24 h, oxidative damage indicated by malondialdehyde (MDA), 8-epi-PGF2α, and 8-hydroxy-2′-deoxyguanosine (8-oxo-dG) concentrations and protein levels of heat shock protein A1A (HSPA1A) and heme oxygenase 1 (HO-1) were determined. Ag NPs induced dose-dependent increases in MDA, 8-epi-PGF2α, and 8-oxo-dG concentrations in both A549 and HepG2 cells. Stress-inducible HSPA1A and HO-1 were also significantly upregulated in a dose-dependent manner. A higher level of HSPA1A and HO-1 activation by Ag NPs occurred in HepG2 cells than that in A549 cells. Compared with that of HSPA1A, Ag NPs induced a stronger increase in protein level of HO-1 in both cell lines. Significant positive correlations between protein levels of HSPA1A and HO-1 and oxidative damage were also observed. In conclusion, Ag NPs could induce oxidative stress in human cell lines. In addition to the products of oxidative stress such as MDA and 8-oxo-dG, HSPs can be used as potential biomarkers in nanotoxicity assessment, especially HO-1.