Altered non-coding RNA expression profile in F1 progeny 1 year after parental irradiation is linked to adverse effects in zebrafish.

Gamma radiation produces DNA instability and impaired phenotype. Previously, we observed negative effects on phenotype, DNA methylation, and gene expression profiles, in offspring of zebrafish exposed to gamma radiation during gametogenesis. We hypothesize that previously observed effects are accompanied with changes in the expression profile of non-coding RNAs, inherited by next generations. Non-coding RNA expression profile was analysed in F1 offspring (5.5 h post-fertilization) by high-throughput sequencing 1 year after parental irradiation (8.7 mGy/h, 5.2 Gy total dose). Using our previous F1-γ genome-wide gene expression data (GSE98539), hundreds of mRNAs were predicted as targets of differentially expressed (DE) miRNAs, involved in pathways such as insulin receptor, NFkB and PTEN signalling, linking to apoptosis and cancer. snRNAs belonging to the five major spliceosomal snRNAs were down-regulated in the F1-γ group, Indicating transcriptional and post-transcriptional alterations. In addition, DEpiRNA clusters were associated to 9 transposable elements (TEs) (LTR, LINE, and TIR) (p = 0.0024), probable as a response to the activation of these TEs. Moreover, the expression of the lincRNAs malat-1, and several others was altered in the offspring F1, in concordance with previously observed phenotypical alterations. In conclusion, our results demonstrate diverse gamma radiation-induced alterations in the ncRNA profiles of F1 offspring observable 1 year after parental irradiation.

Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon.

Ionizing radiation is a recognized genotoxic agent, however, little is known about the role of the functional form of DNA in these processes. Post translational modifications on histone proteins control the organization of chromatin and hence control transcriptional responses that ultimately affect the phenotype. The purpose of this study was to investigate effects on chromatin caused by ionizing radiation in fish. Direct exposure of zebrafish (Danio rerio) embryos to gamma radiation (10.9 mGy/h for 3h) induced hyper-enrichment of H3K4me3 at the genes hnf4a, gmnn and vegfab. A similar relative hyper-enrichment was seen at the hnf4a loci of irradiated Atlantic salmon (Salmo salar) embryos (30 mGy/h for 10 days). At the selected genes in ovaries of adult zebrafish irradiated during gametogenesis (8.7 and 53 mGy/h for 27 days), a reduced enrichment of H3K4me3 was observed, which was correlated with reduced levels of histone H3 was observed. F1 embryos of the exposed parents showed hyper-methylation of H3K4me3, H3K9me3 and H3K27me3 on the same three loci, while these differences were almost negligible in F2 embryos. Our results from three selected loci suggest that ionizing radiation can affect chromatin structure and organization, and that these changes can be detected in F1 offspring, but not in subsequent generations.

Radiation biology of Caenorhabditis elegans: germ cell response, aging and behavior.

The study of radiation effect in Caenorhabditis (C.) elegans has been carried out over three decades and now allow for understanding at the molecular, cellular and individual levels. This review describes the current knowledge of the biological effects of ionizing irradiation with a scope of the germ line, aging and behavior. In germ cells, ionizing radiation induces apoptosis, cell cycle arrest and DNA repair. Lots of molecules involved in these responses and functions have been identified in C. elegans, which are highly conserved throughout eukaryotes. Radiosensitivity and the effect of heavy-ion microbeam irradiation on germ cells with relationship between initiation of meiotic recombination and DNA lesions are discussed. In addition to DNA damage, ionizing radiation produces free radicals, and the free radical theory is the most popular aging theory. A first signal transduction pathway of aging has been discovered in C. elegans, and radiation-induced metabolic oxidative stress is recently noted for an inducible factor of hormetic response and genetic instability. The hormetic response in C. elegans exposed to oxidative stress is discussed with genetic pathways of aging. Moreover, C. elegans is well known as a model organism for behavior. The recent work reported the radiation effects via specific neurons on learning behavior, and radiation and hydrogen peroxide affect the locomotory rate similarly. These findings are discussed in relation to the evidence obtained with other organisms. Altogether, C. elegans may be a good "in vivo" model system in the field of radiation biology.

Appraisal of chemotherapy effects on reproductive outcome according to animal studies and clinical data.

Cancer in women or men during reproductive life raises fears and dilemmas regarding the ability to have a healthy child. Chemotherapy and radiotherapy increase genetic defects in germ cells, depending on the agent used and the stage of gamete maturation. No increase in miscarriage or congenital malformation rates is detected among children born years post-cancer treatment. However, when pregnancy occurred shortly after treatment, increased abortion and malformation risk was reported. Until more data are available, monitoring of chromosomal aberrations and birth defects is recommended. Complexity of cancer treatment is significantly amplified in women exposed to chemotherapy during pregnancy due to concerns regarding direct maternal risks caused by treatment and risk to the developing embryo-fetus. The potential teratogenic effect of cancer treatment depends upon the developmental stage of the fetus at exposure and on drugs used. During the first trimester, abortion and malformation rates are increased, while second- and third-trimester chemotherapy may increase the risk of stillbirth, fetal growth restriction, and premature birth. Maternal myelosuppression increases bleeding and infection tendency, which can harm the fetus. A multidisciplinary team alerted to possible consequences of cancer treatment on pregnancy outcome should provide the optimal treatment options for these patients.

[Regularities of radiation effects in ontogenesis of progeny of the 1st generation of Wistar rats after irradiation of germ cells of both parents at different stages of gametogenesis]. / Zakonomernosti realizatsii luchevykh éffektov v ontogeneze potomstva pervogo pokoleniia krys linii Vistar posle oblucheniia polovykh kletok oboikh roditelei na razlichnykh stadiiakh gametogeneza.

The data on antenatal and postnatal periods of ontogenesis of the posterity of the first generation of Wistar rats exposed by doses of 2-4 Gy at various terms before conception showed that the realization of radiation effects depended on the stage of gametogenesis of sex cells of both parents at radiation exposure. Stimulating radiation effect (hyperovulation) is accompanied by the higher rate of antenatal and early postnatal death of the posterity. In the rest cases it died mainly at embryogenesis. The most unfavourable factor for ontogenesis of the posterity appeared to be a participation in the fertilization of sex cells exposed at postmeiotic stages of gametogenesis, with the degree of manifestation of radiation effects depending on radiation dose.