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- D'Auria Vieira de Godoy, Paulo Roberto, et al.
(författare)
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Effect of dose and dose rate of gamma irradiation on the formation of micronuclei in bone marrow cells isolated from whole-body-irradiated mice
- 2021
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Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 0893-6692 .- 1098-2280. ; 62:7, s. 422-427
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Tidskriftsartikel (refereegranskat)abstract
- It is well-known that the cytotoxicity and mutagenic effects of high dose rate (HDR) ionizing radiation (IR) are increased by increasing the dose but less is known about the effects of chronic low dose rate (LDR). In vitro, we have shown that in addition to the immediate interaction of IR with DNA (the direct and indirect effects), low doses and chronic LDR exposure induce endogenous oxidative stress. During elevated oxidative stress, reactive oxygen species (ROS) react with DNA modifying its structure. Here, BL6 mice were exposed to IR at LDR and HDR and were then sacrificed 3 hours and 3 weeks after exposure to examine early and late effects of IR. The levels of micronuclei, MN, were determined in bone marrow cells. Our data indicate that the effects of 200 mGy on MN-induction are transient, but 500 and 1000 mGy (both HDR and LDR) lead to increased levels of MN up to 3 weeks after the exposure.
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- Lu, Viktor, et al.
(författare)
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The association between serum estradiol levels and sperm DNA integrity
- 2022
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Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 0893-6692 .- 1098-2280. ; 63:6, s. 268-274
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Tidskriftsartikel (refereegranskat)abstract
- In men from the general population, BMI has been associated with a lower sperm DNA fragmentation index (DFI). We wondered whether this could be due to estradiol, which is associated with BMI and reported important for sperm function. Our objective was to investigate the association between estradiol and DFI. In 2008–2010, we recruited 284 young men from the general population to deliver samples of semen and blood and answer questionnaires. Serum concentrations of reproductive hormones and DFI were analyzed, the latter using the Sperm Chromatin Structure Assay. Associations were studied using general linear models. The first model utilized metric values of estradiol, whereas the second model compared men with high and low levels, dichotomized by the median value. A possible interaction between estradiol and testosterone was also examined. When investigating metric estradiol levels and DFI, an inverse association was seen without adjustments (p =.02), but the statistical significance was lost at adjustments for potential confounders (p =.08). Men with lower estradiol levels (<88 pmol/L, mean 71 pmol/L) had a statistically significantly higher DFI than men with higher levels of estradiol (≥88 pmol/L, mean 110 pmol/L). Mean ratio difference was 1.21 (p =.002) without adjustments and 1.18 (p =.01) with adjustments. A statistically significant difference in DFI was observed in men with testosterone levels below median when comparing high and low estradiol (p <.001). This study supports the idea that serum estradiol levels are protective for sperm DNA integrity, at least at lower testosterone levels.
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- Maselli, Bianca S., et al.
(författare)
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Similar polycyclic aromatic hydrocarbon and genotoxicity profiles of atmospheric particulate matter from cities on three different continents
- 2020
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Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 0893-6692 .- 1098-2280. ; 61, s. 560-573
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Tidskriftsartikel (refereegranskat)abstract
- The extractable organic material (EOM) from atmospheric total suspended particles (TSP) contains several organic compounds including non-substituted polycyclic aromatic hydrocarbons (PAHs), alkyl-PAHs, and nitro-PAHs. These chemicals seem to be among the key drivers of TSP genotoxicity. We have shown previously that the mutagenic potencies of the EOM from Limeira, Stockholm, and Kyoto, cities with markedly different meteorological conditions and pollution sources are similar. Here we compare the profiles of non-substituted PAHs (27 congeners), alkyl-PAHs (15 congeners), and nitro-PAHs (7 congeners) from the same EOM samples from these cities. We also compared the genotoxicity profiles using comet and micronucleus assays in human bronchial epithelial cells. The profiles of PAHs, as well as the cytotoxic and genotoxic potencies when expressed in EOM, were quite similar among the studied cities. It seems that despite the differences in meteorological conditions and pollution sources of the cities, removal, mixing, and different atmospheric transformation processes may be contributing to the similarity of the PAHs composition and genotoxicity profiles. More studies are required to verify if this would be a general rule applicable to other cities. Although these profiles were similar for all three cities, the EOM concentration in the atmospheres is markedly different. Thus, the population of Limeira (similar to 10-fold more EOM/m(3) than Stockholm and similar to 6-fold more than Kyoto) is exposed to higher concentrations of genotoxic pollutants, and Kyoto's population is 1.5-fold more exposed than Stockholm's. Therefore, to reduce the risk of human exposure to TSP genotoxins, the volume of emissions needs to be reduced.
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- Felipe de Oliveira Galvão, Marcos, et al.
(författare)
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Determination of whole mixture-based potency factors for cancer risk assessment of complex environmental mixtures by in vitro testing of standard reference materials
- 2022
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 63, s. 98-98
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Tidskriftsartikel (refereegranskat)abstract
- Whole mixture-based testing using in vitro new approach methodologies (NAMs) has been suggested to facilitate the hazard and risk assessment of complex environmental mixtures. Previous studies have shown that phosphorylation of DNA damage signaling proteins checkpoint kinase 1 (pChk1) and histone 2AX (γH2AX) are sensitive markers that can be used for estimating carcinogenicity potencies in vitro. Here, and with the aim to better validate the applicability, in vitro-based Mixture Potency Factors (MPFs) of Standard Reference Materials (SRMs) from environmental polycyclic aromatic hydrocarbon (PAH)-containing mixtures were determined and compared to published mutagenicity and tumorigenicity data. Also, genotoxicity was assessed by a flow cytometry-based micronucleus (MN) assay which showed that only benzo[a]pyrene (B[a]P) and coal tar SRM (SRM1597a) caused dose-dependent increases of MN formation, while extracts of diesel particulate matter (SRM1650b), diesel particulate extract (SRM1975), and urban dust (SRM1649b) did not. However, a dose-dependent activation of DNA damage signaling was observed for all PAHs and SRMs. The results demonstrated that all SRMs were more potent than B[a]P, at B[a]P-equivalent concentrations, to induce pChk1 and γH2AX, and that western blot was more sensitive than the In-Cell Western assay in detecting their activation in response to these complex mixtures. Relative MPFs, based on dose–response modelling of pChk1 and γH2AX, ranged 113 – 5270 for the SRMs, indicating several orders of magnitude higher genotoxic potential than B[a]P. Moreover, these MPFs were in good agreement with potency values based on published data from Salmonella mutagenicity and in vivo carcinogenicity studies. In conclusion, these comparisons further validate the feasibility of applying in vitro NAMs, such as whole-mixture based MPFs, in cancer risk assessment of complex mixtures.
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