Offspring Of Irradiated Parents Research Articles

Contribution of transposable elements to transgenerational effects of chronic radioactive exposure of natural populations of Drosophila melanogaster living for a long time in the zone of the Chernobyl nuclear disaster

The accident at the Chernobyl Nuclear Power Plant (ChNPP) led to the negative impact of chronic radioactive contamination on populations of organisms associated with the transgenerational transmission of genome instability. When the destabilization of genome, different genetic damages occur, the accumulation of which leads to the formation of mutations, morphological anomalies, and mortality in the offspring. The mechanisms underlying the manifestation of transgenerational events in the offspring of irradiated parents are not well understood. In this study, for the first time, the features of the influence of transposable elements (TEs) on the long-term biological consequences of the ChNPP are considered. In this work, specimens of D. melanogaster obtained from natural populations in 2007 in the areas of the ChNPP with heterogeneous radioactive contamination were studied. The descendants from these populations were maintained in laboratory (inbred) conditions for 160 generations. A stable transgenerational transmission of dominant lethal mutations (DLMs) to the offspring of all studied populations was shown. The DLM frequencies strongly were correlated with the level of survival of offspring. The mean frequencies of recessive sex-linked lethal mutations varied at the level of spontaneous point mutations. The simultaneous presence of P, hobo and I elements indicates that the studied populations do not have a definite cytotype, their phenotypic status is unstable. The behavior of TEs in the genomes of offspring depends not only on parental exposure, but also on origin of population, distance to the ChNPP, and inbred conditions. The obtained results confirm the hypothesis that TEs are involved in transgenerational transmission and accumulation of mutations by the offspring of irradiated parents. The TEs pattern present in the Chernobyl genomes of D. melanogaster is a peculiar of epigenetic mechanism for the regulation of plasticity and adaptation of populations living for many generations under conditions of a technogenically caused radiation background.

Involvement of DNA Repair Genes and System of Radiation-Induced Activation of Transposons in Formation of Transgenerational Effects.

The study of the genetic basis of the manifestation of radiation-induced effects and their transgenerational inheritance makes it possible to identify the mechanisms of adaptation and possible effective strategies for the survival of organisms in response to chronic radioactive stress. One persistent hypothesis is that the activation of certain genes involved in cellular defense is a specific response of the cell to irradiation. There is also data indicating the important role of transposable elements in the formation of radiosensitivity/radioresistance of biological systems. In this work, we studied the interaction of the systems of hobo transposon activity and DNA repair in the cell under conditions of chronic low-dose irradiation and its participation in the inheritance of radiation-induced transgenerational instability in Drosophila. Our results showed a significant increase of sterility and locus-specific mutability, a decrease of survival, fertility and genome stability (an increase the frequency of dominant lethal mutations and DNA damage) in non-irradiated F1/F2 offspring of irradiated parents with dysfunction of the mus304 gene which is responsible for excision and post-replicative recombination repair and repair of double-stranded DNA breaks. The combined action of dysfunction of the mus309 gene and transpositional activity of hobo elements also led to the transgenerational effects of irradiation but only in the F1 offspring. Dysfunction of the genes of other DNA repair systems (mus101 and mus210) showed no visible effects inherited from irradiated parents subjected to hobo transpositions. The mei-41 gene showed specificity in this type of interaction, which consists in its higher efficiency in sensing events induced by transpositional activity rather than irradiation.

Effects of long-term radiation exposure to hypertension events in offspring of irradiated parents

Effects of long-term radiation exposure to hypertension events in offspring of irradiated parents

Evidence relevant to untargeted and transgenerational effects in the offspring of irradiated parents.

In this article we review health effects in offspring of human populations exposed as a result of radiotherapy and some groups exposed to chemotherapy. We also assess risks in offspring of other radiation-exposed groups, in particular those of the Japanese atomic bomb survivors and occupationally and environmentally exposed groups. Experimental findings are also briefly surveyed. Animal and cellular studies tend to suggest that the irradiation of males, at least at high doses (mostly 1Gy and above), can lead to observable effects (including both genetic and epigenetic) in the somatic cells of their offspring over several generations that are not attributable to the inheritance of a simple mutation through the parental germline. However, studies of disease in the offspring of irradiated humans have not identified any effects on health. The available evidence therefore suggests that human health has not been significantly affected by transgenerational effects of radiation. It is possible that transgenerational effects are restricted to relatively short times post-exposure and in humans conception at short times after exposure is likely to be rare. Further research that may help resolve the apparent discrepancies between cellular/animal studies and studies of human health are outlined.

THE LONG-TERM CONSEQUANCES OF IRRADIATION OF MALE RATS FOR REPRODUCTIVE FUNCTION OF MALE OFFSPRING AND THEIR RESISTANCE TO THE LOW DOSES IRRADIATION

The evaluation of the reproductive function of irradiated male rat offspring and their resistance to the low doses irradiation has been carried out. Male rats of paternal generation were irradiated by incorporated radionuclides during 45 days and the total absorbed doses (TAD) of males D3, D2 and D1 groups were 3, 9 and 94 mGy in gonads. Offspring from irradiated fathers showed normal sexual behavior. But breeding potential of offspring from fathers with TAD 94 mGy was decreased up to 67,6 % by reason of the increase of intrauterine losses in pregnant female. The sibs were irradiated in the same dose as their fathers (TAD 4 mGy) from 2–2,5 till 6–6,5 months. Breeding potentials of irradiated progeny of irradiated fathers were identical with those of unirradiated sibs. The decrease (on 66 %) of fertility of irradiated in first generation animals (group RA-F1-Control) was found. Discovered changes maybe reflects the adaptation of reproductive function of offspring of irradiated parents to conditions specified by chronic low doses irradiation

THE STATE OF REPRODUCTIVE FUNCTION AND THE RESISTANCE AGAINST THE IRRADIATION FOR FEMALE — PROGENY OF THE IRRADIATED FATHERS

The aim of the study was to estimate the state of reproductive function of irradiated male rat offspring and their resistance against the irradiation in low doses. Male rats of paternal generation were exposed to radiation by incorporated radionuclides during 45 days and the total absorbed doses (TAD) of males D3, D2 and D1 groups were 3, 9 and 94 mGy in gonads. Offspring from fathers with TAD 3–9 mGy had nothing changes in reproduction. But breeding potential of offspring from fathers with TAD 94 mGy was decreased on 41,3 %. Part of sibs was irradiating in the same dose as their fathers (TAD ∼= 4 mGy) since 2–2,5 mounth to 6–6,5 month old. The decrease (on 58,3 %) of fertility of irradiated in first generation animals (group RA-F1-Control) was found. Breeding potential of irradiated progeny of irradiated fathers was come to normal and was better than of their unirradiated sibs. Discovered changes maybe reflects the adaptation of reproductive function of offspring of irradiated parents to conditions of chronic irradiation in low doses.

Radiotherapy for childhood cancer and risk for congenital malformations in offspring: a population‐based cohort study

Offspring of childhood cancer survivors may be at risk of genetic disease due to the mutagenic cancer treatments received by their parents. Congenital malformations were evaluated in a population-based cohort study of 1715 offspring of 3963 childhood cancer survivors and 6009 offspring of 5657 survivors' siblings. The Danish Central Population Register, Cancer Registry and Hospital Register were used to identify study subjects and congenital malformations. Gonadal and uterine radiation doses were characterized based on standard radiation-treatment regimens. The prevalence of congenital malformations at birth in offspring of survivors (44 cases, 2.6%) was slightly higher but not statistically different from that of offspring of siblings (140 cases, 2.3%) [prevalence proportion ratio (PPR), 1.1; 95% confidence interval, 0.8-1.5] or of the general population (observed-to-expected ratio, 1.2; 0.9-1.6). Including malformations diagnosed later in life did not change the ratios appreciably. The risk for malformations was slightly higher in the offspring of irradiated parents than in that of non-irradiated parents (PPR 1.2 vs 1.0) but was unrelated to gonadal dose. This study provides evidence that cancer therapy of children does not increase the risk for malformations in their offspring. Continued monitoring of genetic risks among their offspring, however, is warranted.

Maternal effects of the scid mutation on radiation-induced transgenerational instability in mice

The results of a number of recent studies show that mutation rates in the offspring of irradiated parents are substantially elevated, however, the effect of parental genotype on transgenerational instability remains poorly understood. Here, we have analysed the mutation frequency at an expanded simple tandem repeat (ESTR) locus in the germline and bone marrow of the first-generation male offspring of control and irradiated male mice. The frequency of ESTR mutation was studied in the offspring of two reciprocal matings male symbol scid x female symbol BALB/c and male symbol BALB/c x female symbol scid, which were compared with that in BALB/c mice. In the offspring of the BALB/c x BALB/c and male symbol scid x female symbol BALB/c matings, which were conceived after paternal sperm irradiation, the frequency of ESTR mutation was significantly elevated in both tissues. In contrast, ESTR mutation frequency was only slightly elevated in the offspring of male symbol BALB/c x female symbol scid mating conceived after paternal irradiation. The results of this study suggest that the oocytes of scid females are unable to fully support the repair of double-strand breaks induced in paternal sperm which may in turn result in the elimination of cells/embryos containing high levels of DNA damage, thus partially preventing the manifestation of genomic instability.

Genomic instability in the offspring of irradiated parents: Facts and interpretations

This review is devoted to genomic instability in the offspring of parents that were irradiated or treated with chemical mutagens. The evidence is presented, showing high frequency of cancer diseases and instability of the genome of somatic and germline cells in the offspring of radiation-exposed animals. Possible epigenetic mechanisms of these effects are considered, as well as their significance as components of genetic factors of radiation risk for humans.

Radiation-induced transgenerational alterations in genome stability and DNA damage

Mutation induction in directly exposed cells is currently regarded as the main component of the genetic risk of ionizing radiation for humans. However, recent data on the transgenerational increases in mutation rates in the offspring of irradiated parents indicate that the genetic risk could be greater than predicted previously. Here, we have analysed transgenerational changes in mutation rates and DNA damage in the germline and somatic tissues of non-exposed first-generation offspring of irradiated inbred male CBA/Ca and BALB/c mice. Mutation rates at an expanded simple tandem repeat DNA locus and a protein-coding gene (hprt) were significantly elevated in both the germline (sperm) and somatic tissues of all the offspring of irradiated males. The transgenerational changes in mutation rates were attributed to the presence of a persistent subset of endogenous DNA lesions (double- and single-strand breaks), measured by the phosphorylated form of histone H2AX (gamma-H2AX) and alkaline Comet assays. Such remarkable transgenerational destabilization of the F(1) genome may have important implications for cancer aetiology and genetic risk estimates. Our data also provide important clues on the still unknown mechanisms of radiation-induced genomic instability.

Inheritance of Radiation-Induced Decrement in Ability of Mice to Withstand Protracted Gamma Radiation Stress

There is some evidence that irradiated male mice sustain genetic damage which is transmitted to subsequent generations as a decrement in the mean life span (1). From Selye's studies of phenomena (2), it may be postulated that the mean life span of a mouse population is an indication of the relationship between the population's inherited life potential or adaptation energy and the nonspecific intrinsic and extrinsic stress factors encountered during the life span. If, indeed, this broad generalization is blessed with an element of truth and a decrement in mean life span is inherited by the offspring of irradiated parents, it should be possible to demonstrate a similar decrement in the ability of such offspring to resist other stresses of a somewhat general or nonspecific nature. Among those stressors listed by Selye (2) as being somewhat general or nonspecific are trauma, hemorrhage, extremes of temperature, excessive muscular exercise, anoxia, and ionizing radiation. The purpose of the present study was to determine whether unirradiated offspring from ten generations of irradiated male mice showed a decrement in their ability to withstand protracted Co60 y-radiation used to simulate a nonspecific chronic stress.