The Therapeutic Effect of Acanthopanax senticosus Components on Radiation-Induced Brain Injury Based on the Pharmacokinetics and Neurotransmitters.

Acanthopanax senticosus (AS) is a medicinal and food homologous plant with many biological activities. In this research, we generated a brain injury model by 60Co -γ ray radiation at 4 Gy, and gavaged adult mice with the extract with AS, Acanthopanax senticocus polysaccharides (ASPS), flavones, syringin and eleutheroside E (EE) to explore the therapeutic effect and metabolic characteristics of AS on the brain injury. Behavioral tests and pathological experiments showed that the AS prevented the irradiated mice from learning and memory ability impairment and protected the neurons of irradiated mice. Meanwhile, the functional components of AS increased the antioxidant activity of irradiated mice. Furthermore, we found the changes of neurotransmitters, especially in the EE and syringin groups. Finally, distribution and pharmacokinetic analysis of AS showed that the functional components, especially EE, could exert their therapeutic effects in brain of irradiated mice. This lays a theoretical foundation for the further research on the treatment of radiation-induced brain injury by AS.

Caffeic acid attenuates irradiation-induced hematopoietic stem cell apoptosis through inhibiting mitochondrial damage.

Hematopoietic stem cells (HSCs) are sensitive to ionizing radiation (IR) damage, and its injury is the primary cause of bone marrow (BM) hematopoietic failure and even death after exposure to a certain dose of IR. However, the underlying mechanisms remain incompletely understood. Here we show that mitochondrial oxidative damage, which is characterized by mitochondrial reactive oxygen species overproduction, mitochondrial membrane potential reduction and mitochondrial permeability transition pore opening, is rapidly induced in both human and mouse HSCs and directly accelerates HSC apoptosis after IR exposure. Mechanistically, 5-lipoxygenase (5-LOX) is induced by IR exposure and contributes to IR-induced mitochondrial oxidative damage through inducing lipid peroxidation. Intriguingly, a natural antioxidant, caffeic acid (CA), can attenuate IR-induced HSC apoptosis through suppressing 5-LOX-mediated mitochondrial oxidative damage, thus protecting against BM hematopoietic failure after IR exposure. These findings uncover a critical role for mitochondria in IR-induced HSC injury and highlight the therapeutic potential of CA in BM hematopoietic failure induced by IR.

Establishment and multiparametric-cytogenetic validation of 60Co-gamma-ray induced, phospho-gamma-H2AX calibration curve for rapid biodosimetry and triage management during radiological emergencies.

Exposure to ionizing radiation is unavoidable to our modern developing society as its applications are widespread and increasing with societal development. The exposures may be planned as in medical applications or may be unplanned as in occupational work and radiological emergencies. Dose quantification of planned and unplanned exposures is essential to make crucial decisions for management of such exposures. This study aims to establish ex-vivo dose-response curve for 60Co-gamma-ray induced gamma-H2AX-foci by immunofluorescence using microscopy and flowcytometry with human lymphocytes. This technique has the potential to serve as a rapid tool for dose estimation and triage application during small to large scale radiological emergencies and clinical exposures. Response curves were generated for the dose range 0-4 Gy (at 1, 2, 4, 8, 16, 24, 48, 72 and 96 h of incubation after irradiation) with microscopy and 0-8 Gy (at 2, 4, 8, 16 and 24 h of incubation after irradiation) with flow cytometry. These curves can be applied for dose reconstruction when post exposure sampling is delayed up to 96 h. In order to evaluate Minimum Detection Limit (MDL) of the assay, variation of background frequency of gamma-H2AX-foci was measured in 12 volunteers. To understand the application window of the assay, gamma-H2AX foci decay kinetics has been studied up to 96 h with microscopy and response curves were generated from 1 to 96 hours post exposure. Gamma-H2AX fluorescence intensity decay kinetics was also studied up to 96 h with flow cytometry and response curves were generated from 2 to 24 hours post irradiation. Established curves were validated with dose blinded samples and also compared with standard cytogenetic assays. An inter-comparison of dose estimates was made among gamma-H2AX assay, dicentric aberrations and reciprocal translocations for application window in various dose ranges and time of blood collection after exposures.

Radioprotection of EGCG based on immunoregulatory effect and antioxidant activity against 60Coγ radiation-induced injury in mice.

Excessive reactive oxygen radicals (ROS) produced by ionizing radiation (IR) can cause human body to serious oxidative damage, leading to oxidation-reduction (REDOX) system imbalance and immune system damage. Here, the radioprotection of EGCG was studied through a model of oxidative damage in 60Coγ radiation mice. Firstly, the weights and the main organs indexes of mice, including the liver index, spleen index and pancreas index, indicated preliminarily the safety and protection of EGCG. Then, the radioprotection of EGCG based on immune-regulation on radiation mice was further investigated. Results suggested that EGCG could prevent significantly the immune system damage caused by 60Coγ via increasing the immune organ index, inducing the transformation of spleen cells into T- and B-lymphocytes, and enhancing the macrophage phagocytosis, compared with model group. In addition, EGCG could also protect spleens of radiation mice from 60Coγ-induced the imbalance of REDOX system by enhancing the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), increasing the level of glutathione (GSH), suppressing lipid peroxidation (Malondialdehyde, MDA). The antioxidant enzymes activities of serum and livers were also increased markedly. Taken together, our results indicated that EGCG possessed the excellent potential to serve as a natural radioprotector against IR-induced damage.

Bone Marrow and Peripheral Blood Cells Toxicity of a Single 2.0 Gy Cobalt60 Ionizing Radiation: An Animal Model.

BACKGROUND: Bone marrow is extremely vulnerable to damage caused by radiation therapy. Hence, bone marrow suppression is an important side effect of radiotherapy. Effective use of radiotherapy is therefore compromised by radiation-related injuries. MATERIAL AND METHODS: Six Guinea-pigs were recruited for the study of which three were subjected to total body irradiation with Co60 while the other three served as controls. Bone marrow and peripheral blood samples were collected before and at days 9, 14 and 21, post irradiation. Manual and automated counts were performed for bone marrow nucleated cells and peripheral blood cells respectively. RESULTS: Declining bone marrow cellularity was evident immediately post irradiation. Mean ± SD of marrow cell counted per mm3 were 121,924±281, 87,603±772, 121,367±375 and 122,750±1000 pre-irradiation and days 9, 14 and 21, postirradiation (p-values 0.10, 0.27 and 0.29 respectively). Significant drops in counts were noticed on day 9 post-irradiation for all red cell parameters (p-values <0.05), for Total White Blood Cell Count and Neutrophil count (p-values <0.05) and also on days 14 and 21 for Lymphocytes (p-values <0.05) and on day 21 for Eosinophil/Basophil/Monocytes (p-value <0.05). A significant drop in platelets counts was also noticed on day 9 (p-value <0.05) which significantly increased above pre-irradiation value on day 21. CONCLUSION: Total body irrradiation with Co60 significantly affects the bone marrow with maximum reductions in marrow nucleated cells and peripheral blood cells counts on day 9 post irradiation.

Salivary biochemical markers as potential acute toxicity parameters for acute radiation injury: A study on small experimental animals.

Researchers have been evaluating several biodosimetric/screening approaches to assess acute radiation injury, related to mass causality. Keeping in mind this background, we hypothesized that effect of whole-body irradiation in single fraction in graded doses can affect the secretion of various salivary components that could be used as acute radiation injury/toxicity marker, which can be used in screening of large population at the time of nuclear accidents/disaster. Thirty Sprague Dawley rats treated with whole-body cobalt-60 gamma irradiation of dose 1-5 Gy (dose rate: 0.95 Gy/min) were included in this study. Whole mixed saliva was collected from all animals before and after radiation up to 72 h postradiation. Saliva was analyzed for electrolytes, total protein, urea, and amylase. Intragroup comparison of salivary parameters at different radiation doses showed significant differences. Potassium was significantly increased as the dose increased from 1 Gy to 5 Gy (p < 0.01) with effect size of difference (r > 0.5). Sodium was significantly altered after 3-5 Gy (p < 0.01, r > 0.5), except 1 and 2 Gy, whereas changes in sodium level were nonsignificant (p > 0.5). Urea, total protein, and amylase levels were also significantly increased as the radiation dose increased (p < 0.01) with large effect size of difference (r > 0.5). This study suggests that salivary parameters were sensitive toward radiation even at low radiation dose which can be used as a predictor of radiation injury.

Eight-year follow-up study of three individuals accidentally exposed to (60)Co radiation: Chromosome aberration and micronucleus analysis.

We assessed dose levels and the persistence of chromosomal aberrations and micronuclei in three individuals in the 8 year following accidental (60)Co radiation exposure. Venous blood samples were collected and used for analyses: traditional chromosome aberration (CA) measurement, G-banding, and the cytokinesis-block micronucleus (CBMN) assay. For CA analysis, we scored dicentric chromosomes (dic) and rings (r) in peripheral blood lymphocytes. The radiation doses (Gy) suffered by the individuals were estimated as: 1.79-2.43 (A), 2.36-2.86 (B), 1.58-1.82 (C), based on CA analysis; and 1.8-2.34 (A), 2.52-2.98 (B), 1.53-1.77 (C), based on CBMN frequencies. G-banding analysis was used to record translocations (t), inversions (inv), and deletions (del). Following the accident, unstable CAs reduced gradually, but stable aberrations persisted. Unstable CAs and CBMN may be valuable biomarkers for dose estimation shortly after high-dose radiation accidents, while stable aberrations may be more useful for assessing long-term effects.

Continuous cytogenetic follow-up, over 5 years, of three individuals accidentally irradiated by a cobalt-60 source.

A cobalt-60 irradiation accident occurred in Shanxi, China, on April 11, 2008. Five people were exposed to total-body irradiation ranging from 1.7 to 14.5 Gy. Two victims died post-irradiation, due to acute intestinal radiation sickness (at 62 days) and tuberculosis (at 1.5 year). The other three victims received medical follow-ups and were monitored for 5 years with multiple cytogenetic analyses. Unstable chromosome aberrations, including dicentric and centric rings (dic+r) and the micronucleus frequency in binucleated lymphocytes, were monitored. In addition, G-banding karyotype and fluorescence in situ hybridization (FISH) methods were used to analyze translocations, for exploring chromosome stability and for retrospective dosimetry. The results show that unstable chromosome aberrations (dic+r) declined each year, dropping to about 20-40% of initial levels by the 5th year. A similar trend was observed for the micronucleus frequency. Our results show that the translocation frequencies of the three victims, detected by G-banding karyotype, remained stable for the 5 years. Five years after irradiation, the translocation rates of the three victims (G-banding and FISH analyses) were similar. The retrospective estimated doses, reconstructed based on the translocation frequencies, were consistent with the biological doses estimated at the first day post-irradiation using dic+r. The results of this study indicate that chromosome translocation frequencies can be used as a biological dosimeter and are an excellent index for dose reconstruction.

Efficacy of common decontamination methods for cleaning contaminated wounds.

Emergency preparedness and response for work with hazardous materials, including radiological materials, necessarily have to involve injuries sustained by the workers. Removing radionuclide contamination from wounds in tissue is essential to minimizing the intake of radiological materials and the internal dose to the individual. This study compares the efficacy of common decontamination methods for removal of Co from contaminated wounds inflicted in pig tissue. The decontamination procedures investigated include a commercially available, non-prescription, surfactant-based, non-ionic wound cleanser spray; a physiologic saline solution spray; and a physiologic saline solution pour. Three different types of wounds are examined: smooth incision, jagged cut, and blunt force trauma wounds. The cleanser and saline sprays are more effective at decontaminating all three wounds than the saline pour. Within the statistical limitations of the study, the difference between the cleanser spray and the saline spray is not significant. However, the cleanser spray successfully decontaminates the wound to a lower mean value. The most noticeable impact in the decontamination process appears to be due to the spray pressure employed with the cleanser and saline sprays.

Progenitors mobilized by gamma-tocotrienol as an effective radiation countermeasure.

The purpose of this study was to elucidate the role of gamma-tocotrienol (GT3)-mobilized progenitors in mitigating damage to mice exposed to a supralethal dose of cobalt-60 gamma-radiation. CD2F1 mice were transfused 24 h post-irradiation with whole blood or isolated peripheral blood mononuclear cells (PBMC) from donors that had received GT3 72 h prior to blood collection and recipient mice were monitored for 30 days. To understand the role of GT3-induced granulocyte colony-stimulating factor (G-CSF) in mobilizing progenitors, donor mice were administered a neutralizing antibody specific to G-CSF or its isotype before blood collection. Bacterial translocation from gut to heart, spleen and liver of irradiated recipient mice was evaluated by bacterial culture on enriched and selective agar media. Endotoxin in serum samples also was measured. We also analyzed the colony-forming units in the spleens of irradiated mice. Our results demonstrate that whole blood or PBMC from GT3-administered mice mitigated radiation injury when administered 24 h post-irradiation. Furthermore, administration of a G-CSF antibody to GT3-injected mice abrogated the efficacy of blood or PBMC obtained from such donors. Additionally, GT3-mobilized PBMC inhibited the translocation of intestinal bacteria to the heart, spleen, and liver, and increased colony forming unit-spleen (CFU-S) numbers in irradiated mice. Our data suggests that GT3 induces G-CSF, which mobilizes progenitors and these progenitors mitigate radiation injury in recipient mice. This approach using mobilized progenitor cells from GT3-injected donors could be a potential treatment for humans exposed to high doses of radiation.

Regulation of photosynthetic performance and antioxidant capacity by 6°Co γ-irradiation in Zizania latifolia plants.

The aim of the present work was to investigate the photosynthetic performance and antioxidant enzyme activities in response to γ-irradiation of an aquatic plant Zizania latifolia. The Z. latifolia seedlings at 6-leaf stage were exposed to 25, 50 and 100 Gy of γ rays from a (60)Co source. The growth parameters, chlorophyll contents, photosynthetic gas exchange, chlorophyll fluorescence, malondialdehyde (MDA) content, antioxidant enzyme activities and antioxidant contents were examined at 1-5 weeks post-irradiation (WPI). The results showed that plant height, leaf number and tiller (branch close to ground) number were significantly suppressed by 50 and 100 Gy irradiation at 5, 3-5 and 4-5 WPI, respectively, but they were not significantly different from control by 25 Gy irradiation. Chlorophyll a, chlorophyll b, and total chlorophyll contents were also found to be significantly decreased by irradiation. The net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci) and transpiration rate (Tr) generally declined in a dose-dependent manner. As for the chlorophyll fluorescence parameters, maximum quantum efficiency of PSII photochemistry (Fv/Fm), actual photochemical efficiency of PSII (Φ(PSII)) and photochemical quenching (qP) were observed to be significantly decreased compared to the control at 3 WPI, while non-photochemical quenching (NPQ) significantly increased by 100 Gy. γ-irradiation induced substantial increase in MDA content, ascorbate peroxidase (APX) activity, reduced ascorbate (AsA) content and reduced glutathione (GSH) content, suggesting a protective mechanism of Z. latifolia plant against oxidative stress when exposed to γ-irradiation.

A Bayesian approach to the analysis of quantal bioassay studies using nonparametric mixture models.

We develop a Bayesian nonparametric mixture modeling framework for quantal bioassay settings. The approach is built upon modeling dose-dependent response distributions. We adopt a structured nonparametric prior mixture model, which induces a monotonicity restriction for the dose-response curve. Particular emphasis is placed on the key risk assessment goal of calibration for the dose level that corresponds to a specified response. The proposed methodology yields flexible inference for the dose-response relationship as well as for other inferential objectives, as illustrated with two data sets from the literature.

On the application of an environmental radiological assessment system to an anthropomorphic surrogate.

Recent developments have seen the expansion of the system of radiological protection for humans to one including protection of the environment against detrimental effects of radiation exposure, although a fully developed framework for integration of human and ecological risk assessment for radionuclides is only at an early stage. In the context of integration, significant differences exist between assessment methodologies for humans and the environment in terms of transfer, exposure, and dosimetry. The aim of this elaboration was to explore possible implications of the simplifications made within the system of environmental radiological protection in terms of the efficacy and robustness of dose-rate predictions. A comparison was conducted between human radiological assessment and environmental radiological assessment for an anthropomorphic surrogate, the results for which, produced by both the environmental and human-oriented risk assessment systems, were critically compared and contrasted. The adopted approach split the calculations into several parts, these being 1) physical transfer in an ecosystem, 2) transfer to humans, 3) internal doses to humans, and 4) external doses to humans. The calculations were carried out using both a human radiological assessment and ecological risk assessment system for the same surrogate. The results of this comparison provided indications as to where the 2 systems are amenable to possible integration and where such integration may prove difficult. Initial stage transport models seem to be an obvious component amenable for integration, although complete integration is arguably unattainable as the differences between endpoints mean that the relevant outputs from the models will not be the same. For the transfer and dosimetry components of 2 typical methodologies, it seems that the efficacy of the environmental system is radionuclide-dependent, the predictions given by the environmental system for (90) Sr and (60) Co being unsatisfactory and those for (239) Pu and (210) Po being evidently poor. Integration in this context might take the form of exploring the biokinetic models developed for humans with regard to selected animals and radionuclides. External dose assessment for environmental and human systems provide results for the surrogate that correspond quite closely providing an indication that integration in this regard is perhaps unnecessary.

Effects of (60)Co gamma irradiation on behavior and gill histoarchitecture of giant fresh water prawn Macrobrachium rosenbergii (DE MAN).

Present study was designed to observe the effects of (60)Co gamma radiation in behavioral and histological changes in the gills of giant fresh water prawn Macrobrachium rosenbergii. The adult prawns were irradiated with four different dose levels (3mGy, 30mGy, 300mGy and 3000mGy) and the control group (without irradiation) was maintained separately. Behavioral changes like hyperactivity, loss of balance, reduced swimming rate, slower rate of food intake and convulsions were observed in higher dose levels of 300mGy and 3000mGy. The histological alterations such as accumulated haemocytes in haemocoelic spaces, abnormal gill tips, lifted lamellar epithelium, swollen and fused lamellae, hyperplasic, necrotic, clavate-globate and complete disorganization of lamellae were observed in (60)Co gamma irradiated prawns. Significantly more considerable histological alterations were observed in the highest dose level of 3000mGy, but no mortality was evidenced. This study serves as biomonitoring tool to assess the radiation pollution in the aquatic environment.

Histological variations in liver of freshwater fish Oreochromis mossambicus exposed to 60Co gamma irradiation.

The irradiation effect of (60)Co at the three dose level of 3 mGy, 30 mGy and 300 mGy on the histology of liver of the freshwater fish Oreochromis mossambicus was investigated. The liver of O. mossambicus was dissected out and processed for light microscopy studies. (60)Co exposed O. mossambicus were found to result in several alterations in the histoarchitecture of liver. The alterations included mild congestion of blood vessels, structural alteration, cellular swelling, vacuolation and necrotic liver cells, indicating a definite response to (60)Co irradiation. The results suggest that the liver of O. mossambicus exposed to (60)Co were structurally altered with increasing dose levels. It is to record that alteration in the liver does not affect the physiology, behaviour or lethality of the individuals. Self regulating mechanisms would have influenced the liver to remain sustained. To confirm the same further studies in the direction by increasing dose level is required.

Antioxidant activities of Ganoderma lucidum polysaccharides and their role on DNA damage in mice induced by cobalt-60 gamma-irradiation.

In this study, the radio-protective effects of Ganoderma lucidum polysaccharides (GLP) were investigated in a mouse animal model exposed to (60)Co gamma-irradiation. Each of three batches of mice were divided into five groups (negative control, positive gamma irradiated control, and low, middle and high dosage GLP groups). Different batches of animals were used to evaluate the impact of GLP on peripheral white blood cell count, immune organ index; DNA damage, lipid peroxidation; micronuclei formation, and nucleated cell count in bone marrow induced by (60)Co gamma-irradiation. DNA strand-break and micronuclei frequency were significantly reduced and glutathione peroxidase activity and nucleated cell count in bone marrow were significantly increased by GLP treatment in a dose-dependent manner. GLP intervention also increased the activity of superoxide dismutase and decreased the level of malondialdehyde in middle and high GLP treatment groups. No adverse effects were observed on peripheral white blood cells and immune organ or body weight in either the control groups or GLP treated gamma exposed mice. These findings suggest that GLP possesses marked antioxidant capacity which plays an important role in the prevention of radiation damage in mice induced by (60)Co gamma-irradiation.

Purple sweet potato pigments protect murine thymocytes from 6°Co γ-ray-induced mitochondria-mediated apoptosis.

PURPOSE: Purple sweet potato (PSP) pigments have been widely accepted as antioxidants but their radioprotective effect still remains unclear. In this study we investigated the effect of PSP pigments on 6°Co γ-ray-induced mitochondria-mediated apoptosis in murine thymocytes. MATERIALS AND METHODS: The murine thymocytes were pretreated by PSP pigments before exposure to 4 Gy 6°Co γ-rays. Flow cytometry analysis was used to measure apoptotic cells and mitochondrial membrane potential. Reactive oxygen species (ROS) were detected using 2',7',-dichlorofluorescein diacetate (DCFH-DA) probe and the activity of antioxidant enzymes was tested by biochemical assay after irradiation. Cytochrome c, caspase-3 and poly ADP-ribose polymerase (PARP) were measured by Western blotting. RESULTS: After treatment with PSP pigments and exposure to 4 Gy radiation the apoptosis of thymocytes was reduced and the mitochondrial transmembrane potential was maintained compared to control cells. In the presence of PSP pigments, ROS were reduced and the activities of glutathione peroxidase (GSH-px) and superoxide dismutase (SOD) were protected and in some cases increased. All the pro-apoptotic proteins (cytochrome oxidase, caspase 3 and PARP) decreased in PSP pigments pretreated thymocytes compared to irradiated cells in the absence of PSP pigments. CONCLUSIONS: Pre-treatment with PSP pigments significantly inhibited 6°Co γ-ray-induced mitochondria-mediated apoptosis. This radioprotective effect might be related to ROS scavenging, the enhancement of the activity of antioxidant enzymes, the maintenance of mitochondrial transmembrane potential, and the sequential inhibition of cytochrome c release and downstream caspase and PARP cleavage.

[Cytological and cytogenetic damages of spermatogonial cells in mice in the acute and late periods after irradiation by protons, helium ions, and gamma-rays].

Experiments with small test animals have been carried out to study the survival rate of spermatogenic cells in the acute period after exposure to protons with the energy 9 GeV, helium ions with the energy 4 GeV/nucleon, and 60Co gamma radiation in doses of 0.5-7.5 Gy and the reciprocal translocation frequency in spermatocytes under meiosis at the diakinesis-metaphase-1 stage six months after the exposure of the animals to protons with the energy 50 MeV and 9 GeV, helium ions with the energy 4 GeV/nucleon, and 60Co gamma-radiation in doses of 0.5-4.0 Gy. It is shown that the dependence of the effect on the dose is linear or near to linear for all kinds of radiation used. Relative biological effectiveness coefficients of the accelerated nuclei obtained by correlating equally effective doses of the standard and investigated radiations turned out to be higher in survival rate of type B spermatogonium and amounted to 2.0 and 1.3 for 9 GeV protons and helium ions respectively. At the same time, the use of the nonparametric method to determine the RBE coefficients in the course of finding out the reciprocal translocation frequency in spermatocytes points to an increase in the RBE coefficients of charged particles from 1.0 to 2.0.

Lens opacities in young individuals long after exposure to protracted low-dose-rate gamma radiation in 60Co-contaminated buildings in Taiwan.

The objective of this study was to assess lenticular changes in a young population years after exposure to protracted long-term low-dose-rate gamma radiation in Taiwan. A total of 41 males and 32 females who lived for several years in (60)Co-contaminated buildings and were less than 20 years old at their first ophthalmological examination in 1998 had a similar examination 4.7 +/- 0.5 years later. Lens opacities were examined by slit-lamp biomicroscopy and were scored by the Lens Opacities Classification System III (LOCS III) and a modified subclinical minor focal lens defect (FLD) system. The FLD scores for both eyes were significantly higher than those in the 1998 examinations. Increases in FLD scores compared to those for unexposed subjects occurred particularly in the anterior lens cortex. Increases in FLD scores were also significantly associated with the amount of previous protracted radiation exposure. An exposure-dependent increase in lens opacities was noted years after individuals relocated from the radiocontaminated environment, suggesting that late lenticular changes persisted and progressed in individuals with previous protracted radiation exposure.

Prolonged time to pregnancy in residents exposed to ionising radiation in cobalt-60-contaminated buildings.

OBJECTIVES: Radiation-induced cytogenetic damage in somatic cells has raised concern that low-dose ionising radiation can also damage germ cells and influence gamete production and/or function, resulting in decreased fertility. Time to pregnancy (TTP) was used to investigate whether exposure to gamma-radiation affected fertility among the residents of cobalt-60-contaminated buildings in Taiwan. METHODS: This was a retrospective pregnancy-based study of 357 pregnancies born to 124 exposed couples. Both the cumulative dose and the dose rate for each pregnancy was estimated based on a physical dose reconstruction programme. The comparison population consisted of 612 pregnancies born to 225 couples randomly sampled from the Taiwan general population. Information on TTP was collected by personal interviews. Fecundability ratios (FRs) were calculated with a discrete proportional hazards model. RESULTS: For exposed mothers, fertility decreased significantly when unprotected intercourse began during the period of living in the radiation-contaminated buildings (FR 0.75, 95% CI 0.61 to 0.92). The effect was borderline significant for fathers (FR 0.83, 95% CI 0.68 to 1.02). There was evidence that prolonged TTP was associated with the rate of exposure for both mothers and fathers (tests for trend: female, p=0.0006; male, p=0.03), especially evident for dose rates > or =10 mSv/year (female, FR 0.60, 95% CI 0.43 to 0.84; male, FR 0.68, 95% CI 0.49 to 0.96). CONCLUSIONS: Our findings suggest that exposure to low-dose ionising radiation of cobalt-60-contaminated buildings may decrease fertility, especially in females. Fertility declined with increasing concurrent dose but not with cumulative dose.