Genes and Environment最新文献

{"title":"o-Aminoazotoluene, 7,12-dimethylbenz[a]anthracene, and N-ethyl-N-nitrosourea, which are mutagenic but not carcinogenic in the colon, rapidly induce colonic tumors in mice with dextran sulfate sodium-induced colitis","authors":"A. Hakura, Naoki Koyama, Yuki Seki, J. Sonoda, S. Asakura","doi":"10.1186/s41021-022-00240-7","DOIUrl":"https://doi.org/10.1186/s41021-022-00240-7","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2022-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47996388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A local QSAR model based on the stability of nitrenium ions to support the ICH M7 expert review on the mutagenicity of primary aromatic amines.","authors":"Ayaka Furukawa,&nbsp;Satoshi Ono,&nbsp;Katsuya Yamada,&nbsp;Nao Torimoto,&nbsp;Mahoko Asayama,&nbsp;Shigeharu Muto","doi":"10.1186/s41021-022-00238-1","DOIUrl":"https://doi.org/10.1186/s41021-022-00238-1","url":null,"abstract":"<p><strong>Background: </strong>Aromatic amines, often used as intermediates for pharmaceutical synthesis, may be mutagenic and therefore pose a challenge as metabolites or impurities in drug development. However, predicting the mutagenicity of aromatic amines using commercially available, quantitative structure-activity relationship (QSAR) tools is difficult and often requires expert review. In this study, we developed a shareable QSAR tool based on nitrenium ion stability.</p><p><strong>Results: </strong>The evaluation using in-house aromatic amine intermediates revealed that our model has prediction accuracy of aromatic amine mutagenicity comparable to that of commercial QSAR tools. The effect of changing the number and position of substituents on the mutagenicity of aromatic amines was successfully explained by the change in the nitrenium ion stability. Furthermore, case studies showed that our QSAR tool can support the expert review with quantitative indicators.</p><p><strong>Conclusions: </strong>This local QSAR tool will be useful as a quantitative support tool to explain the substituent effects on the mutagenicity of primary aromatic amines. By further refinement through method sharing and standardization, our tool can support the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M7 expert review with quantitative indicators.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"10"},"PeriodicalIF":1.7,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40310712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of maternal exposure to fine particulate matter with preterm and early-term birth in high-risk pregnant women","authors":"Kaixin Cao, Hongyan Jin, Haoxin Li, Mengmeng Tang, Jianhong Ge, Zekang Li, Xiaoyun Wang, Xuetao Wei","doi":"10.1186/s41021-022-00239-0","DOIUrl":"https://doi.org/10.1186/s41021-022-00239-0","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45417347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Tocopherol phosphate as a photosensitizer in the reaction of nucleosides with UV light: formation of 5,6-dihydrothymidine.","authors":"Toshinori Suzuki,&nbsp;Chiaki Ono","doi":"10.1186/s41021-022-00237-2","DOIUrl":"https://doi.org/10.1186/s41021-022-00237-2","url":null,"abstract":"<p><strong>Introduction: </strong>α-Tocopherol phosphate, a natural water-soluble α-tocopherol analog, exists in biological tissues and fluids. Synthesized α-tocopherol phosphate is used as an ingredient of cosmetics.</p><p><strong>Findings: </strong>When a neutral mixed solution of 2'-deoxycytidine, 2'-deoxyguanosine, thymidine, and 2'-deoxyadenosine was irradiated with UV light at wavelengths longer than 300 nm in the presence of α-tocopherol phosphate, thymidine was markedly consumed in an α-tocopherol phosphate dose-dependent manner, whereas other nucleosides only slightly decreased. Two major product peaks were detected in an HPLC chromatogram. The products were identified as diastereomers of 5,6-dihydrothymidine. The addition of radical scavengers had almost no effects on the generation of 5,6-dihydrothymidine, whereas the reactions of nucleosides other than thymidine were suppressed. Trolox, another water-soluble α-tocopherol analog, did not generate 5,6-dihydrothymidine, although all nucleosides were slightly consumed. When UV irradiation of thymidine with α-tocopherol phosphate was conducted in D₂O, two deuterium atoms were added to 5 and 6 positions of thymidine with both syn and anti configurations. The ratio of syn and anti configurations alternated depending on pD of the solution.</p><p><strong>Conclusions: </strong>The results indicate that α-tocopherol phosphate is a photosensitizer of nucleosides, especially thymidine, and that it introduces two hydrogen atoms to thymidine from H₂O, generating 5,6-dihydrothymidine.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"6"},"PeriodicalIF":1.7,"publicationDate":"2022-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8845368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39634094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of nucleotide insertion opposite urea and translesion synthesis across urea by DNA polymerases.","authors":"Taishu Kawada,&nbsp;Katsuhito Kino,&nbsp;Kyousuke Tokorodani,&nbsp;Ryuto Anabuki,&nbsp;Masayuki Morikawa,&nbsp;Takanobu Kobayashi,&nbsp;Kazuaki Ohara,&nbsp;Takayuki Ohshima,&nbsp;Hiroshi Miyazawa","doi":"10.1186/s41021-022-00236-3","DOIUrl":"https://doi.org/10.1186/s41021-022-00236-3","url":null,"abstract":"<p><p>Urea (Ua) is produced in DNA as the result of oxidative damage to thymine and guanine. It was previously reported that Klenow fragment (Kf) exo^- incorporated dATP opposite Ua, and that DNA polymerase β was blocked by Ua. We report here the following nucleotide incorporations opposite Ua by various DNA polymerases: DNA polymerase α, dATP and dGTP (dATP > dGTP); DNA polymerase δ, dATP; DNA polymerase ζ, dATP; Kf exo^-, dATP; Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4), dGTP and dATP (dGTP > dATP); and DNA polymerase η, dCTP, dGTP, dATP, and dTTP (dCTP > dGTP > dATP > dTTP). DNA polymerases β and ε were blocked by Ua. Elongation by DNA polymerases δ and ζ stopped after inserting dATP opposite Ua. Importantly, the elongation efficiency to full-length beyond Ua using DNA polymerase η and Dpo4 were almost the same as that of natural DNA.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"7"},"PeriodicalIF":1.7,"publicationDate":"2022-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8845263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39634092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The establishment, development and future of the Chinese environmental mutagen society.","authors":"Jia Cao","doi":"10.1186/s41021-021-00232-z","DOIUrl":"https://doi.org/10.1186/s41021-021-00232-z","url":null,"abstract":"<p><p>It has been 40 years since the Chinese Environmental Mutagen Society (CEMS) was established in 1981. Now, it has grown a first-level national society in China, which has 15 professional committees and more than 5000 members. Over the past 40 years, the CEMS has been making many contributions to advance the research of environmental mutagens in China and cultivate professional talents in this field. In the twenty-first century, looking back on what the CEMS has gone through and accomplished, and in light of the major changes in our tasks and mission in the new era, we must plan well for the future, to overcome our shortcomings, to embrace greater development of the CEMS.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"5"},"PeriodicalIF":1.7,"publicationDate":"2022-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39855769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reactions of 3',5'-di-O-acetyl-2'-deoxyguansoine and 3',5'-di-O-acetyl-2'-deoxyadenosine to UV light in the presence of uric acid.","authors":"Toshinori Suzuki,&nbsp;Miyu Takeuchi,&nbsp;Atsuko Ozawa-Tamura","doi":"10.1186/s41021-022-00234-5","DOIUrl":"https://doi.org/10.1186/s41021-022-00234-5","url":null,"abstract":"<p><strong>Introduction: </strong>Recently, it was revealed that uric acid is a photosensitizer of reactions of nucleosides on irradiation with UV light at wavelengths longer than 300 nm, and two products generated from 2'-deoxycytidine were identified. In the present study, UV reactions of acetylated derivatives of 2'-deoxyguansoine and 2'-deoxyadenosine were conducted and their products were identified.</p><p><strong>Findings: </strong>Each reaction of 3',5'-di-O-acetyl-2'-deoxyguansoine or 3',5'-di-O-acetyl-2'-deoxyadenosine with UV light at wavelengths longer than 300 nm in the presence of uric acid generated several products. The products were separated by HPLC and identified by comparing UV and MS spectra of the products with previously reported values. The major products were spiroiminodihydantoin, imidazolone, and dehydro-iminoallantoin nucleosides for 3',5'-di-O-acetyl-2'-deoxyguansoine, and an adenine base and a formamidopyrimidine nucleoside for 3',5'-di-O-acetyl-2'-deoxyadenosine.</p><p><strong>Conclusions: </strong>If these damages caused by uric acid with sunlight occur in DNA of skin cells, mutations may arise. We should pay attention to the genotoxicity of uric acid in terms of DNA damage to dGuo and dAdo sites mediated by sunlight.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"4"},"PeriodicalIF":1.7,"publicationDate":"2022-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39847550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1,3-Butadiene: a ubiquitous environmental mutagen and its associations with diseases.","authors":"Wan-Qi Chen,&nbsp;Xin-Yu Zhang","doi":"10.1186/s41021-021-00233-y","DOIUrl":"https://doi.org/10.1186/s41021-021-00233-y","url":null,"abstract":"<p><p>1,3-Butadiene (BD) is a petrochemical manufactured in high volumes. It is a human carcinogen and can induce lymphohematopoietic cancers, particularly leukemia, in occupationally-exposed workers. BD is an air pollutant with the major environmental sources being automobile exhaust and tobacco smoke. It is one of the major constituents and is considered the most carcinogenic compound in cigarette smoke. The BD concentrations in urban areas usually vary between 0.01 and 3.3 μg/m³ but can be significantly higher in some microenvironments. For BD exposure of the general population, microenvironments, particularly indoor microenvironments, are the primary determinant and environmental tobacco smoke is the main contributor. BD has high cancer risk and has been ranked the second or the third in the environmental pollutants monitored in most urban areas, with the cancer risks exceeding 10^-5. Mutagenicity/carcinogenicity of BD is mediated by its genotoxic metabolites but the specific metabolite(s) responsible for the effects in humans have not been determined. BD can be bioactivated to yield three mutagenic epoxide metabolites by cytochrome P450 enzymes, or potentially be biotransformed into a mutagenic chlorohydrin by myeloperoxidase, a peroxidase almost specifically present in neutrophils and monocytes. Several urinary BD biomarkers have been developed, among which N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine is the most sensitive and is suitable for biomonitoring BD exposure in the general population. Exposure to BD has been associated with leukemia, cardiovascular disease, and possibly reproductive effects, and may be associated with several cancers, autism, and asthma in children. Collectively, BD is a ubiquitous pollutant that has been associated with a range of adverse health effects and diseases with children being a subpopulation with potentially greater susceptibility. Its adverse effects on human health may have been underestimated and more studies are needed.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"3"},"PeriodicalIF":1.7,"publicationDate":"2022-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39669938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of hepatocarcinogens by combination of liver micronucleus assay and histopathological examination in 2-week or 4-week repeated dose studies.","authors":"Shuichi Hamada,&nbsp;Miyuki Shigano,&nbsp;Yumi Wako,&nbsp;Kazufumi Kawasako,&nbsp;Kensuke Satomoto,&nbsp;Tatsuya Mitsumoto,&nbsp;Takayuki Fukuda,&nbsp;Wakako Ohyama,&nbsp;Takeshi Morita,&nbsp;Makoto Hayashi","doi":"10.1186/s41021-021-00222-1","DOIUrl":"https://doi.org/10.1186/s41021-021-00222-1","url":null,"abstract":"<p><strong>Background: </strong>Currently, revisions to the ICH S1 guidance on rodent carcinogenicity testing are being proposed. Application of this approach would reduce the use of animals in accordance with the 3Rs principles (reduce/refine/replace). The method would also shift resources to focus on more scientific mechanism-based carcinogenicity assessments and promote safe and ethical development of new small molecule pharmaceuticals. In the revised draft, findings such as cellular hypertrophy, diffuse and/or focal cellular hyperplasia, persistent tissue injury and/or chronic inflammation, preneoplastic changes, and tumors are listed as histopathology findings of particular interest for identifying carcinogenic potential. In order to predict hepatocarcinogenicity of test chemicals based on the results from 2- or 4-week repeated dose studies, we retrospectively reanalyzed the results of a previous collaborative study on the liver micronucleus assay. We focused on liver micronucleus induction in combination with histopathological changes including hypertrophy, proliferation of oval cells or bile duct epithelial cells, tissue injuries, regenerative changes, and inflammatory changes as the early responses of hepatocarcinogenesis. For these early responses, A total of 20 carcinogens, including 14 genotoxic hepatocarcinogens (Group A) and 6 non-liver-targeted genotoxic carcinogens (Group B) were evaluated.</p><p><strong>Results: </strong>In the Group A chemicals, 5 chemicals (NPYR, MDA, NDPA, 2,6-DNT, and NMOR) showed all of the 6 early responses in hepatocarcinogenesis. Five chemicals (DMN, 2,4-DNT, QUN, 2-AAF, and TAA) showed 4 responses, and 4 chemicals (DAB, 2-NP, MCT, and Sudan I) showed 3 responses. All chemicals exhibited at least 3 early responses. Contrarily, in the Group B chemicals (6 chemicals), 3 of the 6 early responses were observed in 1 chemical (MNNG). No more than two responses were observed in 3 chemicals (MMC, MMS, and KA), and no responses were observed in 2 chemicals (CP and KBrO3).</p><p><strong>Conclusion: </strong>Evaluation of liver micronucleus induction in combination with histopathological examination is useful for detecting hepatocarcinogens. This assay takes much less time than routine long-term carcinogenicity studies.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"2"},"PeriodicalIF":1.7,"publicationDate":"2022-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39786961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of risk due to chronic low dose ionizing radiation exposure on the birth prevalence of congenital heart diseases (CHD) among the newborns from high-level natural radiation areas of Kerala coast, India.","authors":"K R Sudheer,&nbsp;P K Mohammad Koya,&nbsp;Anu J Prakash,&nbsp;Ambily M Prakash,&nbsp;R Manoj Kumar,&nbsp;S Shyni,&nbsp;C K Jagadeesan,&nbsp;G Jaikrishan,&nbsp;Birajalaxmi Das","doi":"10.1186/s41021-021-00231-0","DOIUrl":"https://doi.org/10.1186/s41021-021-00231-0","url":null,"abstract":"<p><strong>Background: </strong>The human population residing in monazite bearing Kerala coast are exposed to chronic low dose and low dose rate external gamma radiation due to Th232 deposits in its beach sand. The radiation level in this area varies from < 1.0 to 45.0 mGy/year. This area serves as an ideal source for conducting large-scale epidemiological studies for assessing risk of low dose and low dose rate radiation exposure on human population. The areas with a dose level of ≤1.50 mGy/year are considered as normal level natural radiation areas (NLNRAs) and areas with > 1.50 mGy/year, as high level natural radiation areas (HLNRAs). HLNRAs were further stratified into three dose groups of 1.51-3.0 mGy/year, 3.01-6.00 mGy/year and > 6.0 mGy/year. The present study evaluates the effects of chronic low dose radiation (LDR) exposure on the birth prevalence of Congenital Heart Diseases (CHD) among the live newborns monitored in hospital based prospective study from NLNRAs and HLNRAs of Kerala coast, India.</p><p><strong>Methodology: </strong>Consecutive newborns were monitored from two hospital units located in the study area for congenital malformations. Referred CHD cases among the newborns screened were confirmed by conducting investigations such as pulse oximetry, chest X-ray, electrocardiogram and echocardiogram etc. RESULTS: Among the newborns screened, 289 CHDs were identified with a frequency of 1.49‰ among 193,634 livebirths, which constituted 6.03% of overall malformations and 16.29% of major malformations. Multiple logistic regression analysis suggested that the risk of CHD among the newborns of mothers from HLNRAs with a dose group of 1.51-3.0 mGy/year was significantly lower as compared to NLNRA (OR = 0.72, 95% CI: 0.57-0.92), whereas it was similar in HLNRA dose groups of 3.01-6.00 mGy/year (OR = 0.55, 95% CI: 0.31-1.00) and ≥ 6.0 mGy/year (OR = 0.96, 95% CI: 0.50-1.85). The frequency of CHDs did not show any radiation dose related increasing trend. However, a significant (P = 0.005) reduction was observed in the birth prevalence of CHDs among the newborns from HLNRA (1.28‰) as compared to NLNRA (1.79‰).</p><p><strong>Conclusion: </strong>Chronic LDR exposure did not show any increased risk on the birth prevalence of CHDs from high-level natural radiation areas of Kerala coast, India. No linear increasing trend was observed with respect to different background dose groups. The frequency of CHD was observed to be 1.49 per 1000 livebirths, which was similar to the frequency of severe CHD rate reported elsewhere in India and was much less than the reported frequency of 9 per thousand.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"1"},"PeriodicalIF":1.7,"publicationDate":"2022-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39646225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}