The use of the embryo‐culture techniques in the research on the Teratogenic and Mutagenic properties of metals†

Actually, embryos can be cultured from the one‐cell stage up to the blastocyst stage, and their development can be easily monitored at any time: severe effects caused by toxic compounds are traduced by rapid embryonic death, less pronounced effects can be expressed by a lowered cleavage activity or by an arrest of the development from a particular stage. The system can be improved by transferring the embryos at the blastocyst stage in another more complete medium where they can “implant”; and form an inner cell mass with differentiated ectoderm and endoderm. Since last years, it has also become possible to culture postimplantation rodent embryos for short periods involving a number of particularly critical stages of organogenesis, such as the formation and closure of the anterior neuropore. Embryo‐culture also represents a useful system to study cytogenetic effects of chemicals which are often linked to lethal or teratogenic effects. These different possibilities are illustrated by examples of studies already performed with metals, and dealing with their teratogenic and/or cytogenetic effects on pre‐ and postimplantation rodents.     

Unexpected phenotypes of malformations induced in Xenopus tropicalis embryos by combined exposure to triphenyltin and 9-cis-retinoic acid

Xenopus tropicalis embryos were exposed for 48 hr to the mixtures of 5 g Sn/L triphenyltin(TPT), which is a well-known endocrine disruptor, and 0.25–5 g/L 9-cis retinoic acid(9c-RA), which is the natural ligand of retinoid X receptor. The phenotypes induced by combined exposure were more variable than those resulting from single exposure to either TPT or 9c-RA. The prominent phenotypes included underdeveloped head structures, abnormal eyes, narrow fins, enlarged proctodaeum, etc. Especially, combined exposure induced unexpected notochord malformations, which ranged from small swellings of the surface of the tails to the extension and extrusion of notochord out of the posterior tails. Compared with the 5 g Sn/L TPT-treated group, the index of fin deficiency was not affected, and the index of axis deficiency was significantly increased with increasing RA concentrations in the mixtures. Our results suggest that combined exposure to TPT and 9c-RA induced not only more variable phenotypes of malformations than exposure to single compound but also some new and unexpected phenotypes.     

A teratological assessment of four trihalomethanes in the rat

Abstract

Four trihalomethanes were administered by gavage to Sprague‐Dawley rats from day 6 to day 15 of gestation. Chloroform (Ch) was administered at levels of 100, 200 and 400 mg/kg and bromoform (Br), bromodichloromethane (BDCM) and chlorodibromomethane (CDBM) were administered at levels of 50, 100 or 200 mg/kg/day. A separate control was used for each compound. Maternal weight gain was depressed in all groups receiving Ch and at the highest dose levels of BDCM and CDBM. Ch administration caused decreased maternal hemoglobin and hematocrit values at all dose levels and also produced increased serum inorganic phosphorus and cholesterol at the highest dose. Liver enlagement was observed at all dose levels of Ch but in no other treatment groups. Evidence of a fetotoxic response was observed with Ch, CDBM and Br but not BDCM. No dose‐related histopathological changes were observed in either mothers or fetuses as a result of treatment. None of the chemicals tested produced any teratogenic effects.     

脱氧雪腐镰刀菌烯醇毒理作用研究进展

脱氧雪腐镰刀菌烯醇(DON)是人畜食品中检出率和超标率最高的一种真菌毒素。与核糖体60s亚基的肽基转移酶活性中心结合后会引发核糖体应激反应,诱导细胞凋亡等作用,对肠道、免疫系统造成破坏,并且具有遗传毒性。为今后的研究工作提供参考,笔者将从DON的毒理学机制和对机体的影响角度入手对近几年新的研究成果做综合论述。     

Bioaccumulation of selenium from natural geologic sources in western states and its potential consequences

Ecological impacts of water-quality problems have developed in the western United States resulting from the disposal of seleniferous agricultural wastewater in wetland areas. Overt effects of selenium toxicosis occurred at five areas where deformities of wild aquatic birds were similar to those first observed at Kesterson National Wildlife Refuge in the west-central San Joaquin Valley of California. These areas are: Tulare Lake Bed Area, California, Middle Green River Basin, Utah, Kendrick Reclamation Project Area, Wyoming, Sun River Basin, Montana, and Stillwater Wildlife Management Area, Nevada. Potential for ecological damage is indicated at six more sites in Oregon, Colorado, the Colorado/Kansas border, and South Dakota out of 16 areas in 11 states where biological tissue data were collected. This conclusion is based on the fact that selenium bioaccumulated in bird livers to median levels that had exceeded or were in the range associated with adverse reproductive effects. Selenium concentrations in samples of fish and bird eggs support these conclusions at a majority of these areas. Reason for concern is also given for the lower Colorado River Valley, although this is not exclusively a conclusion from these reconnaissance data. Biogeochemical conditions and the extent of selenium contamination of water, bottom sediment, and biota from which this assessment was made are given here. In a companion paper, the biogeochemical pathway postulated for selenium contamination to take place from natural geologic sources to aquatic wildlife is defined.     

Histological observation on unique phenotypes of malformation induced in Xenopus tropicalis larvae by tributyltin

Tributyltin (TBT), a biocide used in antifouling paints, has shown strong teratogenic effects on Xenopus tropicalis embryos at environmentally relevant concentrations. X. tropicalis embryos were exposed to 50, 100 and 200 ng/L tributyltin chloride for 72 hr. The histological changes were further observed on abnormal eyes, enlarged trunks, enlarged proctodaeums and absence of fins induced by TBT. The lens and the retinal layers of abnormal eyes were slightly or barely differentiated, and that the pigment epithelium was neither continuous nor smooth. The abdomens were full of undifferentiated gut tissue with yolk-rich inclusions in the tadpoles with enlarged trunks. The proctodaeums formed a bump-like or columnar structure. The mass of yolk-rich cells occupied the lumen, blocked the opening and even turned inside out of the proctodaeum. Both the ventral and dorsal fins in trunks and tails became narrow or even disappeared totally. Our results suggest that great changes of histology took place corresponding to the unique phenotypes. The gut tissue was poorly differentiated, which led to the failed elongation of the guts and subsequently the enlarged trunks. The enlarged proctodaeums were due to the undifferentiation of inner layer, the expansion of outer epidermal part and the absence of fins around them. In brief, the histological observations provided insights into the reason of the unique external malformations in some degree.     

用水螅再生试验预测化学物致畸性的研究

通过亚硝酸钠,苯甲酸钠,氧化钠,青霉素钠,以及丙酮酸钠对水螅的毒性实验和对水螅再生试验应用于预测化学物致畸性的可行性,实验结果表明,亚硝酸钠,苯甲酸钠、氟化钠除了对水螅和再生体产生毒性作用外,还具有一定的致畸性,而青霉素钠和丙酮酸钠未显示出致畸性,与哺乳动物的致畸性试验结果相吻合,初步表明水螅再生试验在筛选在预测化学物致畸性方面有一定的应用价值。     

Assessing the toxicity and teratogenicity of pond water in north-central minnesota to amphibians

BACKGROUND: Incidence of amphibian deformities have increased in recent years, especially in the northern region of the United States. While many factors have been proposed as being responsible for generating deformities (e.g., contaminants, ultraviolet radiation [UV], parasites), no single cause has been definitively established. METHODS: To determine whether waterborne chemicals are responsible for amphibian deformities in ponds in north-central Minnesota, we deployed semipermeable membrane devices (SPMDs) in an impacted and a reference site to accumulate lipophilic contaminants. We then exposed native tadpoles (northern leopard frogs; Rana pipiens) to the SPMD extracts combined with two agricultural pesticides (atrazine, carbaryl) at two levels of UV radiation. RESULTS AND DISCUSSION: UV radiation alone caused a slight increase in hatching success and tadpole growth rate. Deformity rate among hatchlings was high following exposure to SPMD extracts from the reference site in the absence of UV, suggesting that chemicals present at this site are broken down by UV to less harmful forms, or become less bioavailable. Conversely, impacted site SPMD extracts caused hatchling deformities only in the presence of UV, suggesting that UV potentiates the teratogenicity of the compounds present there. Impacted site SPMD extracts significantly increased the number of bony triangles among metamorphs, a common deformity observed at this site. The incidence of skin webbings increased significantly with SPMD extracts from both sites as well as with our pesticide control containing atrazine and carbaryl alone. CONCLUSIONS: Higher deformity rates among tadpoles reared in the presence of UV radiation and SPMD extracts from sites where deformities are common indicates a chemical compound (or compounds) in the water at this site may be causing the deformities. RECOMMENDATIONS AND OUTLOOK: It is important to examine the effects of chemical stressors in the presence of other natural stressors (e.g., UV radiation) to gain a better understanding of how multiple stressors work to impact amphibians and amphibian populations.     

农药麦病治的毒性研究

本文报道麦病治的毒理研究结果。急性毒性试验表明，麦病治为低毒物质，蓄积毒性试验Ｋ＞５，为弱蓄积性。体外致突变试验结果表明，麦病治无致基因突变作用。体内细胞水平试验未见到有致骨髓嗜多染红细胞微核率升高的作用。生殖系统致突变试验表明，麦病治不会导致生殖细胞的染色体损伤，对ＳＤ系大鼠的生殖能力及胎鼠的生长发育均未见不良影响，对胎鼠外观、骨骼内脏无致畸作用。