BackgroundDNA polymerase κ (Polk), a member of Y-family DNA polymerases, plays an important role in translesion DNA synthesis (TLS), allowing DNA replication forks to bypass DNA damage or DNA adducts to continue daughter strand synthesis. Polk is also believed to contribute to the replication-independent repair of DNA lesions such as cross-links. TLS circumvents stalls of DNA replication and promotes gap filling in DNA repair which would otherwise result in DNA double-strand breaks (DSBs) and cell death. Mitomycin C (MMC) is a widely used chemotherapeutic drug which generates DNA cross-links and induces DSBs. To clarify how Polk contributes to the prevention of MMC-induced DSB in various organs or tissues, immunohistochemical staining of γH2AX was conducted in catalytically inactivated Polk knock-in (Polk KI) mice and Polk wild-type (Polk+) mice treated with MMC or saline.ResultsThe γH2AX induction by MMC was enhanced by inactivation of Polk across many organs or tissues to varying degrees. Obvious enhancement was observed in liver, bladder, adrenal cortex, thyroid, and spermatids, whereas less enhancement was shown in brain and retina. The results suggest that Polk plays a role in preventing DSBs caused by MMC in most organs or tissues. Elevated DSB frequencies were observed in both proliferative cells, such as bladder epithelium cells, and less or slowly proliferative cells, such as hepatocytes. Increased DSB levels in inactivated Polk KI mice relative to Polk+ mice were also observed in saline-treated mice in the adrenal cortex and other tissues.ConclusionPolk plays a systemic role in mitigating MMC-induced DSBs, likely through both DNA replication-dependent and -independent mechanisms. Furthermore, Polk appears to protect against DSBs caused by endogenous mutagens in some organs such as the adrenal cortex, prostate, and retina.Supplementary InformationThe online version contains supplementary material available at 10.1186/s41021-025-00343-x.

This article outlines the history and development of Genes and Environment, the official journal of the Japanese Environmental Mutagen and Genome Society (JEMS). In the 1970s, there was growing concern about the mutagenicity of chemical substances, leading to the establishment of JEMS. The society began publishing its journal, Environmental Mutagen Research, and renamed Genes and Environment in 2006 to focus on gene-environment interactions and promote international collaboration. The journal transitioned to free-access and started publishing in English to expand its reach globally.From 2012, the journal partnered with BioMed Central (BMC) to become an open-access publication, leading to its inclusion in Scopus, PubMed, and SCIE, and an improvement in its CiteScore and Impact Factor. JEMS also sought funding from Japan’s Grants-in-Aid for Scientific Research (KAKENHI) to support international dissemination of research.Despite progress, challenges remain, such as limited submissions from certain regions and a need for greater global recognition. To further internationalize JEMS, efforts are being made to elevate the quality of research and broaden membership diversity, with a focus on making JEMS’ activities and publications more accessible to the global scientific community.

BackgroundSkin is exposed to various environmental factors throughout life, and some of these factors are known to contribute to skin aging. Long-term solar UV exposure is a well-known cause of skin aging, as is cigarette smoke, which contains a number of chemicals. In this study, combined effect of UVA and cigarette sidestream smoke (CSS) on matrix metalloproteinase-1 (MMP-1) induction was investigated. MMP-1 is the main protease that initiates collagen type I fiber fragmentation in human skin and is associated with aging.ResultsCombined exposure to UVA and CSS enhanced MMP-1 induction, accompanied by collagen type I (COL1A1) gene suppression. The basal expression of MMP-1 was higher in senescent cells than in normal cells, with a pronounced increase after coexposure to UVA and CSS. UVA irradiation resulted in global histone H3 acetylation, and we considered this was responsible for the MMP-1 upregulation. Histone deacetylase inhibitors, sodium acetate, propionate, and butyrate, all enhanced the CSS-induced MMP-1 according to the degree of histone acetylation.ConclusionThese results suggest that UVA and CSS additively induce MMP-1, which may lead to skin aging, and that such combined effect may further promote aging in aged skin. UVA-induced histone acetylation may contribute to MMP-1 induction.

BackgroundThe Escherichia coli MutT (NudA) protein catalyzes the hydrolysis of an oxidized form of dGTP, 8-oxo-7,8-dihydro-dGTP (8-hydroxy-dGTP), and the spontaneous mutation frequency is elevated in E. coli cells deficient in the mutT gene.ResultsA split MutT, comprising the N-terminal (residues 1–95) and C-terminal (residues 96–129) peptides, was designed based on the known tertiary structure and linker insertion mutagenesis experiments. The mutator phenotype was complemented when the two peptides were separately expressed in mutT E. coli cells.ConclusionsThese results indicated that this split MutT functions as a nucleotide pool sanitization enzyme in vivo.

BackgroundExposure to chemical mixtures inherent in air pollution, has been shown to be associated with the risk of breast and lung cancers. However, studies on the molecular mechanisms of exposure to a mixture of these pollutants, such as hydrocarbons, in the development of breast and lung cancers are scarce. We utilized in silico toxicogenomic analysis to elucidate the molecular pathways linked to both cancers that are influenced by exposure to a mixture of selected hydrocarbons. The Comparative Toxicogenomics Database and Cytoscape software were used for data mining and visualization.ResultsTwenty-five hydrocarbons, common in air pollution with carcinogenicity classification of 1 A/B or 2 (known/presumed or suspected human carcinogen), were divided into three groups: alkanes and alkenes, halogenated hydrocarbons, and polyaromatic hydrocarbons. The in silico data-mining revealed 87 and 44 genes commonly interacted with most of the investigated hydrocarbons are linked to breast and lung cancer, respectively. The dominant interactions among the common genes are co-expression, physical interaction, genetic interaction, co-localization, and interaction in shared protein domains. Among these genes, only 16 are common in the development of both cancers. Benzo(a)pyrene and tetrachlorodibenzodioxin interacted with all 16 genes. The molecular pathways potentially affected by the investigated hydrocarbons include aryl hydrocarbon receptor, chemical carcinogenesis, ferroptosis, fluid shear stress and atherosclerosis, interleukin 17 signaling pathway, lipid and atherosclerosis, NRF2 pathway, and oxidative stress response.ConclusionsWithin the inherent limitations of in silico toxicogenomics tools, we elucidated the molecular pathways associated with breast and lung cancer development potentially affected by hydrocarbons mixture. Our findings indicate adaptive responses to oxidative stress and inflammatory damages are instrumental in the development of both cancers. Additionally, ferroptosis—a non-apoptotic programmed cell death driven by lipid peroxidation and iron homeostasis—was identified as a new player in these responses. Finally, AHR potential involvement in modulating IL-8, a critical gene that mediates breast cancer invasion and metastasis to the lungs, was also highlighted. A deeper understanding of the interplay between genes associated with these pathways, and other survival signaling pathways identified in this study, will provide invaluable knowledge in assessing the risk of inhalation exposure to hydrocarbons mixture. The findings offer insights into future in vivo and in vitro laboratory investigations that focus on inhalation exposure to the hydrocarbons mixture.

BackgroundDNA damage response (DDR) and repair are vital for safeguarding genetic information and ensuring the survival and accurate transmission of genetic material. DNA damage, such as DNA double-strand breaks (DSBs), triggers a response where sensor proteins recognize DSBs. Information is transmitted to kinases, initiating a sequence resulting in the activation of the DNA damage response and recruitment of other DDR and repair proteins to the DSB site in a highly orderly sequence. Research has traditionally focused on individual protein functions and their order, with limited quantitative analysis, prompting this study’s attempt at absolute quantification of DNA damage response and repair proteins and capturing changes in protein chromatin affinity after DNA damage through biochemical fractionation methods.ResultsTo assess the intracellular levels of proteins involved in DDR and repair, multiple proteins associated with different functions were quantified in EPC2-hTERT cells. H2AX had the highest intracellular abundance (1.93 × 106 molecules/cell). The components of the MRN complex were present at the comparable levels: 6.89 × 104 (MRE11), 2.17 × 104 (RAD50), and 2.35 × 104 (NBS1) molecules/cell. MDC1 was present at 1.27 × 104 molecules/cell. The intracellular levels of ATM and ATR kinases were relatively low: 555 and 4860 molecules/cell, respectively. The levels of cellular proteins involved in NHEJ (53BP1: 3.03 × 104; XRCC5: 2.62 × 104; XRCC6: 5.05 × 105 molecules/cell) were more than an order of magnitude higher than that involved in HR (RAD51: 2500 molecules/cell). Furthermore, we analyzed the dynamics of MDC1 and γH2AX proteins in response to DNA damage induced by the unstable agent neocarzinostatin (NCS). Using cell biochemical fractionation, cells were collected and analyzed at different time points after NCS exposure. Results showed that γH2AX in chromatin fraction peaked at 1 h post-exposure and gradually decreased, while MDC1 translocated from the isotonic to the hypertonic fraction, peaking at 1 hour as well. The study suggests increased MDC1 affinity for chromatin through binding to γH2AX induced by DNA damage. The γH2AX-bound MDC1 (in the hypertonic fraction) to γH2AX ratio at 1 h post-exposure was 1:56.4, with lower MDC1 levels which may attributed to competition with other proteins.ConclusionsThe approach provided quantitative insights into protein dynamics in DNA damage response.

The number of breast cancer patients is increasing worldwide. Furthermore, breast cancer often develops in young people, even those only in their 30s, who play a central role in their families and society. Results from many cohort studies suggest that dietary factors, alcohol consumption, lack of physical activity, obesity, nulliparity, breastfeeding, oral contraceptive use, fertility treatment and hormone replacement therapy are risk factors for breast cancer. However, the effects of lifestyle habits on the human body are complexly intertwined with various factors, and the effects vary from person to person depending on their constitution, etc., so there is no basis for this. Therefore, primary prevention of breast cancer is still not being implemented appropriately and efficiently. Furthermore, advances in genomic technology make it possible to assess the risk of developing breast cancer in some individuals. As a result, the establishment of breast cancer prevention methods has become a health priority for high-risk individuals.Drugs such as tamoxifen and raloxifene are known to prevent the development of breast cancer, based on the results of multiple randomized controlled trials, but there are concerns regarding the side effects of these powerful agents. In addition, several clinical studies have shown that prophylactic mastectomy for women who have BRCA mutations or who are identified as being at high risk reduces the incidence of breast cancer development. However, many issues, such as changes in long-term quality of life after preventive surgery, the optimal timing of surgery and the identification of women who are at high risk but will not develop breast cancer, remain uncertain. In other words, although many researchers have focused on chemoprevention and surgical prevention and clear preventive effects of these strategies have been confirmed, it cannot be said that they are widely accepted. Therefore, the current evidence for chemoprevention and surgical prevention, as well as highlights of several interesting lines of research currently underway, are summarized in this article.

BackgroundMutagenicity, the ability of chemical agents to cause mutations and potentially lead to cancer, is a critical aspect of substance safety assessment for protecting human health and the environment. Metabolic enzymes activate multiple mutagens in living organisms, thus in vivo animal models provide highly important information for evaluating mutagenicity in human. Rats are considered suitable models as they share a similar metabolic pathway with humans for processing toxic chemical and exhibit higher responsiveness to chemical carcinogens than mice. To assess mutagenicity in rats, transgenic rodents (TGRs) are widely used for in vivo gene mutation assays. However, such assays are labor-intensive and could only detect transgene mutations inserted into the genome. Therefore, introducing a technology to directly detect in vivo mutagenicity in rats would be necessary. The next-generation sequencing (NGS) based error-corrected sequencing technique is a promising approach for such purposes.ResultsWe investigated the applicability of paired-end and complementary consensus sequencing (PECC-Seq), an error-corrected sequencing technique, for detecting in vivo mutagenicity in the rat liver samples. PECC-Seq allows for the direct detection of ultra-rare somatic mutations in the genomic DNA without being constrained by the genomic locus, tissue, or organism. We tested PECC-Seq feasibility in rats treated with diethylnitrosamine (DEN), a mutagenic compound. Interestingly, the mutation and mutant frequencies between PECC-Seq and the TGR assay displayed a promising correlation. Our results also demonstrated that PECC-Seq could successfully detect the A:T > T:A mutation in rat liver samples, consistent with the TGR assay. Furthermore, we calculated the trinucleotide mutation frequency and proved that PECC-Seq accurately identified the DEN treatment-induced mutational signatures.ConclusionsOur study provides the first evidence of using PECC-Seq for in vivo mutagenicity detection in rat liver samples. This approach could provide a valuable alternative to conventional TGR assays as it is labor- and time-efficient and eliminates the need for transgenic rodents. Error-corrected sequencing techniques, such as PECC-Seq, represent promising approaches for enhancing mutagenicity assessment and advancing regulatory science.

ObjectiveThe aim of this study was to assess the correlation of spouse selection with short tandem repeats (STRs) in DNA and with the number of fingertip lunulae to investigate the role of heredity in spouse selection.MethodsWe randomly selected a total of 286 couples (husband and wife) as a couple group while 200 paired subjects (a man randomly matched with a woman as a pair of subjects) were selected as a non-spouse group for DNA typing, and to investigate lunulae in spouse selection, a total of 554 couples were selected as a couple group and 500 pairs of subjects were selected as a control group.ResultsA significant difference of STR matching number (a large value implies a higher genetic similarity) between spouse group and non-spouse group were observed (12.3 ± 2.7 vs. 11.8 ± 2.6; p < 0.05). A significant difference of the lunula matching number (difference of lunula counts between a paired subjects, a lower value implies a higher genetic similarity) between two groups were also observed for the lunula counts (1.55 ± 1.88 vs. 3.53 ± 2.40; p < 0.01).ConclusionSignificant and unprecedented relationships were found between the couples and polymorphic STRs, and between spouse selection and lunula counts. Polymorphic STRs and fingertip lunulae counts provide an initial insight into the potentially important contributions that genetic characteristics may play a key role in spouse selection.

BackgroundHelicobacter pylori secretes cytotoxin-associated gene A (CagA) into the gastric epithelium, causing gastric mucosal atrophy (GMA) and gastric cancer. In contrast, host cells degrade CagA via autophagy. However, the association between polymorphisms in autophagy-related genes and GMA must be fully elucidated.ResultsWe evaluated the association between single nucleotide polymorphisms (SNPs) in autophagy-related genes (low-density lipoprotein receptor-related protein 1, LRP1; capping actin protein of muscle Z-line alpha subunit 1, CAPAZ1; and lysosomal-associated membrane protein 1, LAMP1) and GMA in 200 H. pylori-positive individuals. The frequency of the T/T genotype at rs1800137 in LRP1 was significantly lower in the GMA group than in the non-GMA group (p = 0.018, odds ratio [OR] = 0.188). The frequencies of the G/A or A/A genotype at rs4423118 and T/A or A/A genotype at rs58618380 of CAPAZ1 in the GMA group were significantly higher than those in the non-GMA group (p = 0.029 and p = 0.027, respectively). Multivariate analysis revealed that C/C or C/T genotype at rs1800137, T/A or A/A genotype at rs58618380, and age were independent risk factors for GMA (p = 0.038, p = 0.023, and p = 0.006, respectively). Furthermore, individuals with the rs1800137 C/C or C/T genotype of LRP1 had a 5.3-fold higher susceptibility to GMA. These genetic tests may provide future directions for precision medicine for individuals more likely to develop GMA.ConclusionLRP1 and CAPZA1 polymorphisms may be associated with the development of GMA.