Selenium Thresholds for Fish from Cold Freshwaters

A review of reproductive effects studies with cold-water fish species including trout (cutthroat, brook, rainbow), white sucker, and northern pike indicates that they have higher tolerances to selenium taken up via dietary sources than warm-water fish species. The USEPA (2004) USEPA (U.S. Environmental Protection Agency). 2004. Draft Aquatic Life Water Quality Criteria for Selenium—2004, Washington, DC, , USA: Office of Water. EPA-822-D-04-001 [Google Scholar] draft Se tissue criterion of 7.9 mg/kg dw will provide a conservative level of protection for these cold-water fish species. However, site- and species-specific studies are required to set realistically protective upper guideline values.     

Egg Selenium Concentrations as Predictors of Avian Toxicity

Aquatic birds are exposed to selenium through their diet by ingesting aquatic invertebrates that have accumulated selenium from water and the food chain. However, dietary composition is highly variable among species, over time, and across sites, making it difficult to provide accurate estimations of dietary exposure for particular species at specific locations. Selenium accumulates in the egg, resulting in embryo malformation, embryonic death, and decreased survival of juveniles. If the relationship between egg concentration and these reproductive parameters can be defined with sufficient certainty, then risk assessments can be performed through analysis of egg selenium concentrations. Other researchers have proposed egg toxicity thresholds that lead to conclusions of widespread selenium toxicoses in waterbirds. However, we believe these values are overly conservative and that it is unlikely that selenium is posing a significant risk to wild birds in areas where the current water quality criterion is being met. Through the use of simple statistical models (logit, probit, and Weibull functions) we are able to express mortality and teratogenicity relationships for mallards (Anas platyrhynchos) in such a manner that the risk manager can be presented with information about the probability of reduced duckling survival if mean egg selenium (MES) concentrations are known. Data analysis indicates that the two endpoints (mortality and teratogenesis) cannot be distinguished statistically. Commonly used effects thresholds (the EC₁₀ and EC₂₀) correspond to 16 and 21?mg/kg dw MES using the most sensitive endpoint, chick mortality. Both of these values are higher than the 6?mg/kg dw level proposed by Skorupa (1998) who based his estimate on field-observational data potentially confounded by other environmental stress factors. The mortality and teratogenicity endpoints presented here relate selenium exposure to risk to individuals within a population and do not provide information about the probability of selenium causing changes in population growth rates, either at the local or regional levels.     

Mercury Toxicity and the Mitigating Role of Selenium

Mercury is a well-known environmental toxicant, particularly in its most common organic form, methylmercury. Consumption of fish and shellfish that contain methylmercury is a dominant source of mercury exposure in humans and piscivorous wildlife. Considerable efforts have focused on assessment of mercury and its attendant risks in the environment and food sources, including the studies reported in this issue. However, studies of mercury intoxication have frequently failed to consider the protective effects of the essential trace element, selenium. Mercury binds to selenium with extraordinarily high affinity, and high maternal exposures inhibit selenium-dependent enzyme activities in fetal brains. However, increased maternal dietary selenium intakes preserve these enzyme activities, thereby preventing the pathological effects that would otherwise arise in their absence. Recent evidence indicates that assessments of mercury exposure and tissue levels need to consider selenium intakes and tissue distributions in order to provide meaningful risk evaluations.     

Selenium Health Benefit Values as Seafood Safety Criteria

Selenium (Se) is absolutely required for activity of 25–30 genetically unique enzymes (selenoenzymes). All forms of life that have nervous systems possess selenoenzymes to protect their brains from oxidative damage. Homeostatic mechanisms normally maintain optimal selenoenzyme activities in brain tissues, but high methylmercury (MeHg) exposures sequester Se and irreversibly inhibit selenoenzyme activities. However, nutritionally relevant amounts of Se can replace the Se sequestered by MeHg and maintain normal selenoenzyme activities, thus preventing oxidative brain damage and other adverse consequences of MeHg toxicity. Findings of studies that seem contradictory from MeHg exposure perspectives are entirely consistent from MeHg:Se molar ratio perspectives. Studies that have reported dose-dependent consequences of maternal MeHg exposures on child development uniformly involved seafoods that contained much more Hg than Se. Meanwhile more typical varieties of ocean fish contain much more Se than Hg. This may explain why maternal MeHg exposure from eating ocean fish is associated with major IQ benefits in children instead of harm. Therefore, instead of being avoided, ocean fish consumption should be encouraged during pregnancy. However, the safety of freshwater fish consumption is less certain. In freshwater fish, MeHg bioaccumulation and toxicity are both inversely related to Se bioavailability. Their Se can be far lower than their MeHg contents, potentially making them more dangerous than pilot whale meats. Therefore, to provide accurate and appropriate regulatory advice regarding maternal consumption of seafoods and freshwater fish, Hg:Se molar ratios need to be incorporated in food safety criteria.     

Rationale and Procedures for Using the Tissue-Residue Approach for Toxicity Assessment and Determination of Tissue,Water, and Sediment Quality Guidelines for Aquatic Organisms

This article describes a set of procedures for developing tissue, water, and sediment quality guidelines for the protection of aquatic life by using the tissue-residue approach (TRA) for toxicity assessment. The TRA, which includes aspects of the Critical Body Residue (CBR) approach, associates tissue concentrations of chemicals with adverse biological effects in a dose-response fashion that can be used to determine CBRs. These CBRs can then be used to develop tissue quality guidelines (TQGs), which may be translated into water or sediment guidelines with bioaccumulation factors. Not all toxicants are amenable to this type of analysis; however, some appear to exhibit relatively consistent results that can likely be applied in a regulatory framework. By examining tissue residues, variations in toxicokinetics (temporal aspects of accumulation, biotransformation, and internal distribution) are greatly reduced allowing a greater focus on toxicodynamics (action and potency) of the toxicants. The strongest feature of this approach is causality; hence, guidelines based on tissue concentrations are based on data demonstrating a causal relationship between the acquired dose and the biological effect. Because the TRA has utility for assessing the toxicity of contaminant mixtures, an approach is presented here using toxic unit values that can be used to assess the likelihood of observing toxic effects based on tissue residues.     

Comparative Toxicity of Three Organic Acids to Freshwater Organisms and Their Impact on Aquatic Ecosystems

The comparative toxicity of lactic acid, acetic acid, and benzoic acid to tilapia (Oreochromis mossambicus), cladoceran crustacea (Moina micrura), and oligochaete worm (Branchiura sowerbyi) were determined using static bioassay tests. Worms were found most sensitive to all the acids whereas the cladoceran was found most resistant to lactic acid and the fish most resistant to acetic acid and benzoic acid. The 96h LC₅₀ values of lactic acid, acetic acid, and benzoic acid, were, respectively, 257.73, 272.87, and 276.74 mg L^?1 for O. mossambicus; 329.12, 163.72, and 71.65 mg L^?1 for M. micrura and 50.82, 14.90, and 39.47 mg L^?1 for B. sowerbyi. Tilapia lost appetite at sub-lethal concentrations as low as 2.18 mg L^?1 lactic acid, 1.26 mg L^?1 acetic acid, and 13.84 mg L^{? 1} of benzoic acid. Growth and reproduction of the fish were affected following 90-day chronic exposure to sub-lethal concentrations of the acids. Minimum effective concentration of the acids that significantly reduced food conversion efficiency (FCE), percent increase of weight, specific growth rate, yield and fecundity of the fish were 2.18, 1.47, and 3.95 mg · L^?1 of lactic acid, acetic acid, and benzoic acid, respectively. Effects of acetic acid and benzoic acid on FCE, weight increase, and yield were not significantly different from each other whereas lactic acid produced different effects from acetic acid as well as benzoic acid. Mean values of dissolved oxygen, primary productivity, and plankton populations of the test medium significantly reduced from control at 16.94 mg L^?1 lactic acid, 16.79 mg L^?1 acetic acid, and 13.84 mg L^?1 benzoic acid.     

Factors in Fish Modifying Methylmercury Toxicity and Metabolism

We report here some results of a long-term (19 month) study with cats fed methylmercury (MeHg) in nutritionally balanced diets based on fish. By using either freshwater pike (low in Se) or canned tuna (high in Se) as the major protein source, basal diets with low levels of MeHg were prepared having different Se content, all Se being of natural origin. The basal diets produced no signs of toxicity or pathological changes over the l9-month period. In cats fed basal diets spiked with medium or high levels of MeHg, evidence for delayed onset of toxic effects from the added MeHg was observed with the tuna diets compared to pike diets. In brain, muscle, and blood, the activity of GSH peroxidase, a selenoenzyme, was decreased by Hg. In liver, substantial accumulation of Hg with Se occured (molar Hg/Se ratio approximately 1.4 to 1.8) but GSH peroxidase activity was unaffected. We suggest that the coaccumulation of Hg and Se in liver measures the extent to which MeHg has been metabolically transformed by metabolism to Hg++, and inactivated by deposition as a Hg/Se complex of low bioavailability. The accumulation of Hg and Se in liver was much greater in cats fed tuna compared to pike, out of proportion to the relatively small differences in Hg and Se content of the tuna and pike basal diets. Some mechanisms are described by which selenium, vitamin E, and other factors might facilitate MeHg breakdown to inorganic Hg during long term low level exposure to MeHg.     

Acute Toxicity for some Evaporating Aromatic Hydrocarbons for Freshwater Snails and Crustaceans

Some typical and more frequent freshwater invertebrates of running waters were studied to examine the influence of styrene, xylene and benzene on their mortality. Snails Amphimelania holandri FÉR. and Lymnaea stagnalis L. and crustacenas Asellus aquaticus L. and Gammarus fossarum KOCH. , were used in the semi-static test. Compounds were added in volume concentrations of 0.005 to 0.4% v/v. For all concentrations LC₅₀ was calculated by probit method, which demonstrated that mortality depends much more on increased concentrations (depending on the initial concentration) than on the length of exposure. Styrene was the most toxic, followed by xylene and then benzene. The species G. fossarum showed marked sensitivity, followed by A. aquaticus, and the species A. holandri and L. stagnalis showed less sensitivity.     

Insular Freshwater Fish Faunas of Micronesia: Patterns of Species Richness and Similarity

Freshwater fishes are an important but relatively little known component of the highly diverse fish fauna of Micronesia. Localities supporting communities of freshwater fishes include large high islands, with considerable habitat complexity, and smaller low islands, such as atolls and raised coral islands, with limited freshwater habitat. Both types of islands may support species with adult life history styles that are (a) amphidromous and catadromous, (b) euryhaline (often estuarine), or (c) marine species which enter freshwater from time to time. We compared patterns of species richness and similarity between Micronesian localities for amphidromous and catadromous, euryhaline and marine species (ACEM) pooled, and for amphidromous and catadromous species (ACFW). Species richness of both ACEM and ACFW fishes was greatest on larger high islands compared to smaller high and all low islands. Cluster analysis of similarity indices for ACEM species between localities revealed two faunal components: high islands and low islands. High islands were further partitioned into a Caroline Islands cluster and a separate Mariana Islands cluster. Cluster analysis of ACFW species was more complex. One cluster consisted of a low island and a small high island, both in the Carolines chain and with limited freshwater habitat. The second cluster was partitioned into high islands and low islands that reflected influences of both size and geographical location.     

Seasonality in Dietary Shifts in Size-Structured Freshwater Fish Assemblages in Three Reservoirs of Sri Lanka

We studied seasonal changes in feeding habits of size-structured fish assemblages in three freshwater reservoirs in Sri Lanka. We obtained fish samples for diet analysis from three reservoirs during the months of rising water level (RIWL) and receding water level (REWL). During RIWL, peripheral areas with terrestrial/semi-terrestrial macrophytes get inundated, which resulted in increased food availability for macrophyte feeding fish. During REWL, detrital food sources increase due to decaying terrestrial plant material, which has inundated. Based on the dietary habits of individual species in the three reservoirs during RIWL and REWL, it is evident that detritivorous and phytoplanktivorous fish species, which belong to low trophic levels do not show significant variation in dietary habits between the two seasons (e.g. Oreochromis mossambicus, Oreochromis niloticus and Amblypharyngodon melettinus). Stenophagous species such as benthic invertebrate predators (Puntius chola and Puntius dorsalis), macrophytophagous species (Etroplus suratensis and Tilapia rendalli) and zooplanktivorous Hemirhamphus limbatus do not exhibit significant variation in dietary habits between seasons. Also their feeding habits do not vary with body size. Euryphagous species such as Puntius filamentosus on the other hand, exhibit variations in dietary habits between seasons as well as with body size. Stenophagous species, which feed on detritus and phytoplankton and euryphagous species, which exhibit temporal dietary plasticity, are therefore abundant in fish assemblages of these reservoirs.     

Selenium: Mercury Molar Ratios in Freshwater Fish in the Columbia River Basin: Potential Applications for Specific Fish Consumption Advisories

Overdoses of acetaminophen (APAP), a famous and widely used drug, may have hepatotoxic effects. Nanoscience is a novel scientific discipline that provides specific tools for medical science problems including using nano trace elements in hepatic diseases. Our study aimed to assess the hepatoprotective role of selenium nanoparticles (Nano-Se) against APAP-induced hepatic injury. Twenty-four male rats were classified into three equal groups: a control group that received 0.9 % NaCl, an APAP-treated group (oral administration), and a group treated with Nano-Se (10–20 nm, intraperitoneal (i.p.) injection) and APAP (oral administration). APAP overdose induced significant elevations in liver function biomarkers, hepatic lipid peroxidation, hepatic catalase, and superoxide dismutase (SOD), decreased the reduced glutathione (GSH) content and glutathione reductase (GR) activity, and stimulated significant DNA damage in hepatocytes, compared to control rats. Nano-Se administration improved the hepatic antioxidant protection mechanism and decreased cellular sensitivity to DNA fragmentation. Nano-Se exhibits a protective effect against APAP-induced hepatotoxicity through improved liver function and oxidative stress mediated by catalase, SOD, and GSH and decreases hepatic DNA fragmentation, a hepatic biomarker of cell death. Nano-Se could be a novel hepatoprotective strategy to inhibit oxidative stress.     

Infection Status of Freshwater Fish with Metacercariae of Clonorchis sinensis in Korea

This study investigated freshwater fish for their current infection status with metacercariae of Clonorchis sinensis in Korea. Twenty-one species of freshwater fish (n = 677) were collected from 34 regions nationwidely from February 2007 to June 2008. They were individually examined by digestion technique. Eight species of freshwater fish from 17 different regions were recognized positive for the metacercariae of C. sinensis. The positive rates (range of metacercariae number per fish) of fish by the species were as follows: 48% (1-1,142) in Pseudorasbora parva, 60% (1-412) in Pungtungia herzi, 15.7% (1-23) in Pseudogobio esocinus, 29% (1-7) in Acheilognathus intermedia, 21% (1-4) in Odontobutis interrupta, 33% (1-6) in Zacco temmincki, 3.6% (1-4) in Zacco platypus, and 26.3% (1) in Hemibarbus labeo. The two species, P. parva and P. herzi, are able to be the index fish for estimation of C. sinensis transmission in a certain locality. Still several species of freshwater fish are briskly transmitting C. sinensis infection in many riverside areas of southern Korea.     

The Asian Fish Tapeworm Bothriocephalus acheilognathi: a Potential Threat to Native Freshwater Fish Species in Mexico

Introduction of the parasite Bothriocephalus acheilognathi Yamaguti, 1934 with the herbivorous carp Ctenopharyngodon idellus, and other cyprinids, has been documented in almost every continent, except Antarctica. This study presents the current geographical distribution of this cestode in the freshwater fish of Mexico, highlighting infections in autochthonous and endemic species. It compiles existing information and presents original data. B. acheilognathi is widely dispersed among the freshwater fish of Mexico, being recorded to date in 49 fish species from 26 genera, 7 families and 5 orders. B. acheilognathi is reported from Mexico for the first time in Dionda ipni, Notropis celayensis, Yuriria alta, Gambusia vittata, Poecilia butleri, P. mexicana, Poeciliopsis baenschi, Poeciliopsis sp., Cichlasoma cyanoguttatum and C. labridens. The new hosts identified in this study bring the total number of known host species to 102 in 14 families and 7 orders of freshwater fishes around the world. Given its wide distribution among Mexican freshwater fish species, the abundance of the parasite and its high pathogenicity, parasitological data for B. acheilognathi should be considered as an important factor in native fish conservation policies. Biological changes in the freshwater habitats in Mexico caused by the introduction of exotic fish species and their parasites are virtually ubiquitous and extremely difficult to eradicate once established. As such, they should be considered as one of the most serious threats to native fish conservation.     

Environmental and Socioeconomic Constraints to the Development of Freshwater Fish Aquaculture in China

In this article, we provide an overview, on freshwater fish aquaculture in P.R. China, with special emphasis on pond fish culture. We describe the history, ecology (trophic structure and species reared), and technological aspects (including inputs/outputs, yields, labor productivity, and fossil energy use) of freshwater fish production and analyze its role in relation to the socioeconomic context. We discuss the prospects for intensification of production. In China, freshwater fish aquaculture has always been closely linked to cultivation of crops and animal husbandry, that is, feed inputs are in the form of agricultural wastes. The close integration with the farming system at large results in an efficient use of nutrients, low environmental loading, and little dependence on fossil energy inputs. About 7 to 9 different fish species, mainly herbivores, are kept in the same pond and efforts are made to maintain as much as possible the natural mechanisms of matter regulation and energy flows within the pond ecosystem. However, ecological compatibility is paid for by relatively low productivity, both per hectare of waterbody and per hour of labor input. If the throughput of freshwater fish production per unit of area and labor are to be dramatically increased, the equilibrium of the traditional integrated system will be difficult to maintain.     

A Perspective on the Toxicity of Petrogenic PAHs to Developing Fish Embryos Related to Environmental Chemistry

Numerous studies demonstrate polynuclear aromatic hydrocarbons (PAHs) dissolved from weathered crude oil adversely affect fish embryos at 0.5 to 23 μg/l. This conclusion has been challenged by studies that claim (1) much lower toxicity of weathered aqueous PAHs; (2) direct contact with dispersed oil droplets plays a significant role or is required for toxicity; (3) that uncontrolled factors (oxygen, ammonia, and sulfides) contribute substantively to toxicity; (4) polar compounds produced by microbial metabolism are the major cause of observed toxicity; and (5) that based on equilibrium models and toxic potential, water contaminated with weathered oil cannot be more toxic per unit mass than effluent contaminated with fresh oil. In contrast, several studies demonstrate high toxicity of weathered oil; shifts in PAH composition were consistent with dissolution (not particle ablation), embryos accumulated dissolved PAHs at low concentrations and were damaged, and assumed confounding factors were inconsequential. Consistent with previous empirical observations of mortality and weathering, temporal shifts in PAH composition (oil weathering) indicate that PAHs dissolved in water should (and do) become more toxic per unit mass with weathering because high molecular weight PAHs are more persistent and toxic than the more abundant low molecular weight PAHs in whole oil.     

Critical Levels of Selenium in Different Crops Grown in an Alkaline Silty Loam Soil Treated with Selenite-Se

Critical levels of selenium in raya (Brassica juncea Czern L.), maize (Zea mays L.), wheat (Triticum aestivum L.) and rice (Oryza sativa L.) were worked out by growing these crops in an alkaline silty loam soil treated with different levels of selenite-Se ranging from 1 to 25 μg g⁻¹ soil. Significant decrease in dry matter yield was observed above a level of 5 μg Se g⁻¹ soil in raya and maize; 4 μg Se g⁻¹ soil in wheat and 10 μg Se g⁻¹ soil in rice shoots. The critical level of Se in plants above which significant decrease in yield would occur was found to be 104.8 μg g⁻¹ in raya, 76.9 μg g⁻¹ in maize, 41.5 μg g⁻¹ in rice and 18.9 μg g⁻¹ in wheat shoots. Significant coefficients of correlation were observed between Se content above the critical level and dry matter yield of raya as well as rice (r = −0.99, P ≤ 0.01), wheat (r = −0.97, P ≤ 0.01) and maize ((r = −0.96, P ≤ 0.01). A synergistic relationship was observed between S and Se content of raya (r = 0.96, P ≤ 0.01), wheat (r = 0.89, P ≤ 0.01), rice (r = 0.85, P ≤ 0.01) and maize (r = 0.84, P ≤ 0.01). Raya, maize and rice absorbed Se in levels toxic for animal consumption (i.e. > 5 mg Se kg⁻¹) when the soil was treated with more than 1.5 μg Se g⁻¹. In case of wheat, application of Se more than 3 μg g⁻¹ soil resulted in production of toxic plants.     

Selenium and Mercury in Native and Introduced Fish Species of Patagonian Lakes,Argentina

A survey of mercury (Hg) and selenium (Se) contents was performed in fish collected from lakes located in two National Parks of the northern patagonian Andean range. Two native species, catfish (Diplomystes viedmensis) and creole perch (Percichthys trucha), and three introduced species, brown trout (Salmo trutta), rainbow trout (Oncorhynchus mykiss), and brook trout (Salvelinus fontinalis), were caught from lakes Nahuel Huapi, Moreno, Traful, Espejo Chico, and Guillelmo belonging to Nahuel Huapi National Park and from lakes Futalaufquen and Rivadavia, Los Alerces National Park. In lake Moreno, fish diet items were analyzed and rainbow trout grown in a farm. Hg and Se were measured in muscle and liver tissues by instrumental neutron activation analysis. The average concentrations in muscle of Hg for all species, ages, and lakes are between 0.4 to 1.0 μg g⁻¹ dry weight (DW) with a few fish, mainly native, exceeding the United States Environmental Protection Agency health advisory for freshwater fish limited consumption, and from 0.8 to 1.5 μg g⁻¹ DW for Se. Average concentrations in liver of Hg in all species range from 0.4 to 0.9 μg g⁻¹ DW. Brown trout, the top predator in these lakes, showed the lowest average Hg burden in both tissues. Se concentrations in the liver of brown and rainbow trout, up to 279 μg g⁻¹ DW, are higher than those expected for nearly pristine lakes, exceeding 20 μg g⁻¹ DW, the threshold concentration associated with Se toxicity. These species show lower Hg contents in muscle, suggesting a possible detoxification of Hg by a Se-rich diet. Creole perch and velvet catfish livers have lower Se concentrations, with a narrower span of values (2.3 to 8.5 μg g⁻¹ and 3.3 to 5.5 μg g⁻¹ DW respectively).     

A Proposed Structure of Modified Nucleosides Expected to Have High Antiviral Activity and Low Toxicity

This article describes modified nucleosides with deactivated 3′-OH and modified at two or more positions. These are expected to have high antiviral activity as well as have low toxicity.     

Selenium Pretreatment Enhances the Radioprotective Effect and Reduces the Lethal Toxicity of Wr-2721

Although WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, is an effective radioprotector, its use is limited by its toxicity. Combining WR-2721 with other agents might decrease its toxicity and/or increase its effectiveness. The effect of selenium (Se) pretreatment on the acute toxicity and radioprotective effect of WR-2721 was studied in male CD2F1 mice. Injection of 1.6mg/kg Se 24 hr before WR-2721 (800-1200 mg/kg, IP) decreased the lethality of WR-2721 significantly. Lower doses of Se were also effective, but simultaneous administration was not effective. Se injection alone (1.6 mg/kg) 24 hr before cobalt-60 irradiation increased the survival (dose reduction factor, DRF = 1.1) significantly. A synergistic effect on post-irradiation survival was observed when Se was injected 24 hr before WR-2721 (200-600 mg/ kg IP before irradiation). For example, after exposure to 22 Gy (1 Gy/min), 30-day survival was 100% when mice were treated with both Se and 600mg/kg WR-2721, and was 13% with WR-2721 alone. The DRF after 400 mg/kg WR-2721 was 2.6 with Se compared to 2.2 without Se pretreatment. Alkaline phosphatase activity in bone marrow cells and serum was significantly depressed after treatment with 1.6 mg/kg Se, suggesting that a retardation of conversion of WR-2721 to its active free sulfhydryl form through the action of alkaline phosphatase might be partly responsible for the effects of Se. Other possible mechanisms related to the antioxidant properties of Se are under investigation.     

Selenium Pretreatment Enhances the Radioprotective Effect and Reduces the Lethal Toxicity of Wr-2721

Although WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, is an effective radioprotector, its use is limited by its toxicity. Combining WR-2721 with other agents might decrease its toxicity and/or increase its effectiveness. The effect of selenium (Se) pretreatment on the acute toxicity and radioprotective effect of WR-2721 was studied in male CD2F1 mice. Injection of 1.6mg/kg Se 24 hr before WR-2721 (800-1200 mg/kg, IP) decreased the lethality of WR-2721 significantly. Lower doses of Se were also effective, but simultaneous administration was not effective. Se injection alone (1.6 mg/kg) 24 hr before cobalt-60 irradiation increased the survival (dose reduction factor, DRF = 1.1) significantly. A synergistic effect on post-irradiation survival was observed when Se was injected 24 hr before WR-2721 (200-600 mg/ kg IP before irradiation). For example, after exposure to 22 Gy (1 Gy/min), 30-day survival was 100% when mice were treated with both Se and 600mg/kg WR-2721, and was 13% with WR-2721 alone. The DRF after 400 mg/kg WR-2721 was 2.6 with Se compared to 2.2 without Se pretreatment. Alkaline phosphatase activity in bone marrow cells and serum was significantly depressed after treatment with 1.6 mg/kg Se, suggesting that a retardation of conversion of WR-2721 to its active free sulfhydryl form through the action of alkaline phosphatase might be partly responsible for the effects of Se. Other possible mechanisms related to the antioxidant properties of Se are under investigation.