Toxicity Effect of Hg^(2+) and Cr(VI) on Alga Growth in Eutrophic Water

[ Objective] The toxicity effect of Hg^2＋ and Cr（Ⅵ） on alga growth in eutrophic water was studied to provide reference for biomonitoring and bioremediation of eutrophic water. [ Method ] The mother liquid of alga, which was separated from the eutrophic water, were put into the solutions of Hg^2＋ and Cr（Ⅵ） with different concentrations and their mixture solution, respectively. And the toxicity effect of Hg^2＋ and Cr（Ⅵ） on the growth and propagation of alga in eutrophic water was observed. [ Result] The alga in eutrophic water performed rather sensitive to Cr（Ⅵ） and when its concentration was over 1 mg/L, threre was obvious effect on alga growth. The alga was not very sensitive to Hg^2＋ when its concentration was lower, but its toxicity became stronger and stronger when its concentration increased to some extent and the toxicity effect of Cr（Ⅵ） on alga growth was just on the contrary. When the ion concentration was lower than 10 mg/L, the toxicity of Hg^2＋ on alga was lower than that of Cr（Ⅵ）. When the concentration was over 10 mg/L, the toxicity of Hg^2＋ exceeded that of Cr（Ⅵ）. The toxicity of ion mixture solution of Hg^2＋ and Cr（Ⅵ） had synergism inhibition on alga, which could be performed only when the concentration was over 4 mg/L. [ Conclusion] The toxicity of heavy metal on alga not only related to the alga cell, but also related to the concentration of heavy metal ion.

Exposure Level, Toxicity Effects and Health Risk Assessment of Organophosphorus Flame Retardants in Water Environment

Organophosphorus flame retardants(OPFRs) are gradually replacing brominated flame retardants(BFRs), which are widely used in the world. The increasing output of OPFRs and the increasing detection of OPFRs in environmental media have attracted wide attention of scholars at home and abroad. OPFRs are generally semi-volatile, easy to enter the environment and accumulate in organisms,causing potential hazards to the environment and human health. In this paper, the pollution status and toxic effects of OPFRs in aquatic environment were introduced,and the research progress of human health risk caused by them was summarized.The existing problems were pointed out, and the future research was prospected. In the future, the analytical methods of various environmental and biological media should be improved, and comprehensive and in-depth environmental investigation and ecological and health risk assessment should be carried out. Attention should be paid to the effects of combined pollution on organisms and the study of biological acceptability.

Protective Effects of Calcium Antagonists on Cadmium-induced Toxicity in Rats

Protective effects of calcium antagonists, chlorpromazine (CPZ) and nimodepine (NI-MO), on cadmium-induced toxicity were investigated. After giving CdCl2 (0. 44mg Cd/kg,ip), CPZ (5mg/kg, ip) or NIMO (8mg/kg, po) were administered every day to Sprague-Dawley (S. D. ) rats for a week. Then, urinary N- acetyl-β-D- glucosaminidase (NAG ), uri -nary cadmium and bloocl cadmium were measured. The accumulation of cadmium in the kid-ney cortex, content of renal calmodulin, hemoglobin and the ultrastructural damage of proxi-mal convoluted tubules of rats were examined three weeks after the last administration. Re-sults indicated that the calcium antagonists partly protected against toxic effects induced bycadmium in different manners. These data provide further evidence for the new hypothesisthat the cross effect of cadmium and calcium in calmodulin regulated systems may be responsi-ble for the mechanism of cadmium intoxication. 'The results suggested that the calcium antag-onists could be a new and promising approach in the therapy of heavy metaLinduced diseases

Clinical Observation on the Efficacy Enhancing and Toxicity Attenuating Effect of Nuzhen Yangyin Granule to the Anti-Parkinsonism Therapy Mainly with Medopa

Objective: To observe and assess the efficacy enhancing and toxicity attenuating effect of Nuzhen Yangyin Granule (NYG) to the anti-parkinsonism (paralysis agitans) therapy with medopa and ar-tane. Methods: Adopting the randomized double-blinded method, the effect of adding NYG to 30 patients with Parkinsonism in the treated group,

Effect of TCDD on Maternal Toxicity and Chorionic Gonadotropin──Bioactivity in the Immediate Post-implantation Period of Macaque

The purpose of this experiment was to observe the alterations in bioactivity of chorionic gonadotropin (CG) associated with early fetal loss (EFL), induced by the environmental toxin TCDD (2,3,7,8\|tetrachlorodibenzo\| p \|dioxin) in the cynomolgus macaque. Ten of twelve females administered single doses of 1, 2 or 4 μg/kg TCDD on gestational day (GD) 12 had EFL from ten to twenty days later. Seven control animals treated only with the vehicle had normal pregnancies. Blood samples were repeatedly collected for hormone evaluation, from two days before treatment to thirty\|one days following treatment. Immunoreactive monkey chorionic gonadotropin (mCG) was measured in serum using ELISA, and bioactive mCG was measured using a luminescence LH/CG bioassay. No change in immunoreactive mCG levels was detected as a result of TCDD, treatment, but bioactive mCG levels were significantly lower in TCDD\|treated animals compared to controls. This change in bioactivity of mCG was also reflected in the ratio of mCG bioactivity to mCG immunoreactivity (B/I ratio) which began to rise in normal pregnancies by GD 20, but did not rise in TCDD treated animals. These results demonstrate that normal pregnancy in the monkey, as in humans, is characterized by a post\|implantation change in the B/I ratio of CG. These findings therefore suggest that changes in the production of bioactive CG may be used as a biomarker of environmental toxicant exposures which lead to EFL.

Histological Assessment and Transcriptome Analysis Provide Insights into the Toxic Effects of Perfluorooctanoic Acid to Juvenile Half Smooth Tongue Sole Cynoglossus semilaevis

Perfluorooctanoic acid(PFOA)is a widespread synthetic persistent organic pollutant that may enrich along the food chain and affect the growth,development,reproduction,and lipid metabolism of aquatic organisms,particularly the benthic organisms.How-ever,the toxic effects of PFOA on the half-smooth tongue sole Cynoglossus semilaevis,a commercial benthic fish in China,have rarely been reported.Because juvenile fish are sensitive to environmental pollutants,in the present study,histological assessment and tran-scriptome sequencing were performed to determine the short-term impact of PFOA on juvenile half-smooth tongue soles.Histologi-cal analysis showed that PFOA exposure caused hepatocyte rupture,intestinal villi breakage,increased goblet cell count,and brain ab-normal.Transcriptome results showed that some interesting signaling pathways,such as glycolysis/gluconeogenesis,PPAR signaling pathway and GABAergic synapse signaling pathway,were enriched after PFOA exposure.In addition,some metabolic,immune and neural genes were differentially expressed,which including ependymin,hbb1-like and gad 1,and they were up-regulated after 14 days of exposure.Transcriptome results also indicated that half-smooth tongue sole might improve energy metabolism in response to PFOA toxicity after 7 days of exposure.These findings provide a basis for studying the ecological effects of PFOA on marine benthic fishes.

Protective Effects of Certain Natural and Synthetic Complexans on the Toxicity of Chromium and Tin to a N_2-Fixing Cyanobacterium, Anabaena doliolum

The effects of chromium and tin on survival, growth, carbon fixation, nitrate reduction, ammonia assimilation, and nitrogenase activity of a N_2-fixing cyanobacterium, Anabaena doliolum, and their amelioration by synthetic and natural complexans, viz., EDTA, nitrilotriacetic acid (NTA), pyridine dicarboxylic acid (PDA), and citrate, have been studied. Chromium proved to be much more toxic than tin, as it inhibited growth yield (49%), carbon fixation (53%), and nitrate reductase (79%), glutamine synthetase (30%), and nitrogenase activities (77%) at its sublethal concentration, whereas tin induced less inhibition of growth yield (42%), carbon fixation (50%). and nitrate reductase (66%), glutamine synthetase (32.4%), and nitrogenase activities (70%). Despite its inhibitory effects at 10μml^(-1), EDTA supplementation in metal-spiked medium counteracted the toxicity of chromium and tin more significantly than NTA, PDA, and citrate. When supplemented with LD_(50) of Cr, EDTA protected growth, carbon fixation, NR, GS. and Noase, respectively, by 32.6, 50.0, 33.3. 17.7. and 65.4%. However, EDTA-induced restoration of the above parameters at a sublethal concentration of tin was only 30.2, 50.0,28.1, 27.7, and 61.5%, respectively. Although NTA and citrate at 10/μgml^(-1) each were stimulatory to various processes of test cyanobacterium, they were comparatively less effective than EDTA in the amelioration of metal toxicity. On the basis of these observations, a generalized hierarchical sequence of protective efficiency of synthetic and natural cornplexing ligands may be given as EDTA > NTA > citrate > PDA. It seems plausible that the toxicity of various heavy metals may be regulated by a large array of organic complexing agents of the aquatic environment because they possess various metal binding sites. (c) 1989 Academic Press,lnc.

Monitoring bioaccumulation and toxic effects of hexachlorobenzene using the polyurethane foam unit method in the microbial communities of the Fuhe River,Wuhan

Hexachlorobenzene （HCB） is a chlorinated aromatic hydrocarbon that was widely used for seed dressing in prevention of fungal growth on crops, and also as a component of fireworks, ammunition, and synthetic rubbers. Because of its resistance to degradation and mobility, HCB is widely distributed throughout the environment and is accumulated through food chains in different ecosystems. In this study, a preliminary investigation was carried out on the bioaccumulation and the toxic effects of HCB in the microbial （protozoan in particular） communities in the Fuhe River, Wuhan, a water body receiving industrial wastewaters containing HCB and other pollutants, using the standardized polyurethane foam units （PFU） method. Field samples were taken from eight stations established along the Fuhe River in January and August 2006. The concentration ratios of HCB in microbial communities and in water were 9.66-18.64, and the microbial communities accumulated 13.29-56.88 μg/L of HCB in January and 0.82-10.25 μg/L HCB in August. Correlation analysis showed a negative correlation between the HCB contents in the microbial assemblage, and the number of species and the diversity index of the protozoan communities. This study demonstrated the applicability of the PFU method in monitoring the effects of HCB on the level of microbial communities.

Toxicity of perfluorononanoic acid and perfluorooctane sulfonate to Daphnia magna

In order to study toxicological effects of perfluorononanoic acid （PFNA）, perfluorooctane sulfonate （PFOS）, and their mixtures （PFNA/ PFOS） on Daphnia magna （D. magna）, a suite of comprehensive toxicity tests were conducted, including a 48-h acute toxicity test, a 21-day chronic test, a feeding experiment, and a biomarker assay. D. magna were exposed to aqueous solutions of PFNA and PFOS （alone and in combination） at concentrations ranging from 0.008 to 5 mg/L. The survival, growth, and reproduction of D. magna were monitored over a 21- day life cycle. The biomarkers, including acetylcholinesterase （ACHE）, superoxide dismutase （SOD）, and catalase （CAT） activities, were determined after seven days of exposure. PFOS was more toxic than PFNA based on the results of the acute toxicity test. Perfluorinated compounds （PFCs） inhibited both growth and reproduction of D. magna during the testing period. The ingestion rates and the biomarkers, including ACHE, SOD, and CAT activities, were significantly inhibited by PFCs in most cases. Moreover, the combined effects related to the growth and reproduction showed the antagonistic effects of PFCs.

Fairy shrimp Branchinella kugenumaensis displays sensitivity to microplastic exposure

The increasing global concern regarding plastic pollution has prompted the research into the consequences of microplastics(MPs)on aquatic ecosystems.Fairy shrimp Branchinella kugenumaensis are freshwater planktonic organisms that have existed for 250 million years.This study aimed to uncover the harmful effects of MPs,with a particular focus on their size variations(0.1,1,and 5μm),on the fairy shrimp.We focused on how MPs could significantly affect the survival and growth of fairy shrimp.Notably,larger MPs,especially those measuring 5μm,caused higher mortality rates and hindered the growth compared to smaller ones.The impact of MPs continued even subsequent to depuration in clean water.The accumulation of MPs within the intestines of fairy shrimp resulted in intestinal blockages,disrupted excretory functions,and harmed intestinal epithelial cells.Examinations at the histological,cellular,and molecular levels showed that exposure to MPs triggered necroptosis in intestinal cells,accompanied by alterations in pathways related to transcription,translation,digestion,energy metabolism,and neurological functions.Furthermore,the effects of MPs on gene expression and pathways varied based on particle size,with larger MPs having a more significant effect and causing a strong response in xenobiotic biodegradation and metabolism pathways.We suggest that the increasing severity of MPs pollution could pose a significant threat to the survival of fairy shrimp.This study provided vital insights into the complex relationship between microplastics and aquatic organisms,and highlighted the urgent need to address the potential devastating impact of plastic pollution on freshwater ecosystems.Additionally,due to their rapid growth,strong reproductive capacity,sensitivity,and ease of cultivation,fairy shrimp hold the potential candidate to serve as a model organism for studying the effects of MPs and other pollutants on freshwater ecosystems.

Bioaccumulation and Toxicity of Neodymium in the Planarian Dugesia japonica

In this study, the bioaccumulation and toxicity of neodymium （Nd） in pla-narian Dugesia japonica were investigated. The results showed that with the in-creasing dietary Nd supplementation, the concentration of Nd in the planarian showed a significant linear increase and the balance of mineral elements was bro-ken with the decrease of Ca, Fe and Mo, and the increase of K and Mg. The content of soluble proteins and the activities of superoxide dismutase （SOD） and catalase （CAT） decreased with the increase of Nd concentration, while the content of H2O2 rose gradual y. The mortality was directly proportional to the Nd concentra-tion. The results indicated that planarian is a very sensitive aquatic animal to Nd contamination and can be an indicator organism for Nd pol ution.

Toxic Effects of Lanthanum, Cerium, Chromium and Zinc on Potamogeton Malaianus

The toxic effects of rare earth elements such as lanthanum, cerium and heavy metal elements such as chromium, zinc on Potamogeton malaianus Miq. were studied. The results show that the contents of chlorophyll and soluble protein increase to a certain degree and then decrease under La3+ Ce3+ Zn2+ stress, while there is a constantly dropping tendency under Cr6+ stress. The four ions have different effects on protective enzyme systems of Potamogeton malaianus. They can induce rises of the activities of catalase (CAT) and peroxides (POD) at lower concentration, however, with the increase of ions concentration, the activities decline. The change of SOD activity is exactly opposite to that of CAT and POD activity. It falls at first and rises later. An increasing tendency of MDA content appears with the increasing concentration. The toxicities of La3+, Zn2+, Ce3+ and Cr6+ become more serious in the order. The lethal concentration of Cr6+ to Potamogeton malaianus ranges from 0.5 to I mg(-1) that of Ce3+ and Zn2+ ranges from 3 to 5 mg(-1) and that of La3+ ranges from 7 to 10 mg(.)L(-1). The toxic mechanism of La3 + and Ce3+ is similar to that of Cr6+ and Zn2+.

Toxic effects of acetochlor, methamidophos and their combination on nifH gene in soil

Toxic effects of two agrochemicals on nifH gene in agricultural black soil were investigated using denaturing gradient gel electrophoresis （DGGE） and sequencing approaches in a microcosm experiment. Changes of soil nifH gene diversity and composition were examined following the application of acetochlor, methamidophos and their combination. Acetochlor reduced the nifH gene diversity （both in gene richness and diversity index values） and caused changes in the nifH gene composition. The effects of acetochlor on nifH gene were strengthened as the concentration of acetochlor increased. Cluster analysis of DGGE banding patterns showed that nifH gene composition which had been affected by low concentration of acetochlor （50 mg/kg） recovered firstly. Methamidophos reduced nifH gene richness that except at 4 weeks. The medium concentration of methamidophos （150 mg/kg） caused the most apparent changes in nifH gene diversity at the first week while the high concentration of methamidophos （250 mg/kg） produced prominent effects on nifH gene diversity in the following weeks. Cluster analysis showed that minimal changes of nifH gene composition were found at 1 week and maximal changes at 4 weeks. Toxic effects of acetochlor and methamidophos combination on nifH gene were also apparent. Different nifH genes （bands） responded differently to the impact of agrochemicals： four individual bands were eliminated by the application of the agrochemicals, five bands became predominant by the stimulation of the agrochemicals, and four bands showed strong resistance to the influence of the agrochemicals. Fifteen prominent bands were partially sequenced, yielding 15 different nifH sequences, which were used for phylogenetic reconstructions. All sequences were affiliated with the alpha- and beta-proteobacteria, showing higher similarity to eight different diazotrophic genera.

ZnO,TiO_2,SiO_2,and Al_2O_3 Nanoparticles-induced Toxic Effects on Human Fetal Lung Fibroblasts

Objective This study aims to investigate and compare the toxic effects of four types of metal oxide （ZnO, TiO2, SiO2, and Al2O3） nanoparticles with similar primary size （-20 nm） on human fetal lung fibroblasts （HFL1） in vitro.Methods The HFL1 cells were exposed to the nanoparticles, and toxic effects were analyzed by using MTT assay, cellular morphology observation and Hoechst 33 258 staining.Results The results show that the four types of metal oxide nanoparticles lead to cellular mitochondrial dysfunction, morphological modifications and apoptosis at the concentration range of 0.25-1.50 mg/mL and the toxic effects are obviously displayed in dose-dependent manner. ZnO is the most toxic nanomaterials followed by TiO2, SiO2, and Al2O3 nanoparticles in a descending order.Conclusion The results highlight the differential cytotoxicity associated with exposure to ZnO, TiO2, SiO2, and Al2O3 nanoparticles, and suggest an extreme attention to safety utilization of these nanomaterials.

Toxic Effects of Tetrabromobisphenol A on Thyroid Hormones in SD Rats and the Derived-reference Dose

The present study determined the thyroid hormone interference of tetrabromobisphenol A （TBBPA） in Sprague-Dawley （SD） rats, and the derived-reference dose （RfD） of different endpoint effects on mammals based on experimental results and data collection. Based on repeated exposure toxicity tests on mammals and extensive research, the present study used BMDS240 Software to derive a benchmark dose, and analyzed the accuracy and uncertainty, and similarity with other studies. Test results on triiodothyronine （T3）, thyroxine （T4）, and thyroid stimulating hormone （TSH） demonstrated that all the indicators presented a non-monotonous dose-effect relationship clearly, except TSH in male rats exposed to 0-1000 mg/kg BW per day. Therefore, RfDs were derived from different critical effects. In summary, RfD for mammals in the present study was found to be 0.6 mg/kg per day.

Influences of Chloropazine, Nimodipine and Their Combination on the Toxic Effects of Cadmium in Liver and Kidney of Mice

The influences of the calmodulin antagonist chlorpromazine (CPZ), and calcium channel blocker nimodipine (NIMO) and their combination on cadmium (Cd) poisoning of mice were studied. A seties of biochemical parameters including urinary enzyme activities, blood and urine Cd levels, metallothionein (MT) contents in liver and kidney, hepatic ultrastructure and Ca2+ -Mg2+ AT-Pase activity in erythrocyte membrane were determined. Animal models for Cd poisoning were established by peritoneal injection of 1/5 LD50 CdCl2. The experimental groups were protected by administration of CPZ, NIMO and CPZ and NIMO in combination l h before the injection of CdCl2. Five days later, samples were collected for analysis. The data showed that Crs could protect kidney tissue against Cd-induced damage, as the urinary γ-glutamyl traspepti dase (γ- GT ) and N- acetyl-β-D-glucosaminidase (NAG) activities were reduced significantly. There was neither evidence of the protective effect of NIMO on kidney tissue nor an indication of a synergistic effecf of Crs and NIMO.Both CPZ and NIMO showed a considerable protective effect against the deerease in Ca2+ -Mg2+ AT-Pase activity, and a synergistic action was observed. Cd content in blood was reduced significanily by CPZ or the combination of CPZ and NIMO, but elevated by NIMO. Both CPZ and NIMO consideraby increased MT contents in livers and kidneys and ameliorated damaged to the hepatic ultrastructures caused by Cd. The results indicated that these inhibitors could protect mice against the toxic effects of Cd in liver and kidney tissues, while CPZ was more efficient than NIMO. The combination of CPZ and NIMO exerted a synergistic action. The protective action of these two drugs might be relevent to the function of MT.

Investigation of the immune effects of Scutellaria baicalensis on blood leukocytes and selected organs of the chicken＇s lymphatic system

Background： The health of chickens and the welfare of poultry industry are central to the efforts of addressing global food security. Therefore, it is essential to study chicken immunology to maintain and improve its health and to find novel and sustainable solutions. This paper presents a study on investigation of the effect of Scutellaria baicalensis root（SBR） on the immune response of broiler chicken, especially on lymphocytes and heterophils reactivity, regarding their contribution to the development of immunity of the chickens.Methods： The 121-day-old Hubbard Hi-Y male broiler hybrids were randomly assigned to four treatment groups,three SBR supplemented groups（0.5, 1.0, and 1.5% of SBR） and one control group. Each treatment was replicated five times with six birds per replicate pen in a battery brooder. Blood was collected after 3-（rd） and 6-（th）wk of the experiment, and hemoglobin and hematocrit values were determined, as well as total leukocyte count and differential count were performed. Nitroblue tetrazolium test and phagocytosis assay as nonspecific immune parameters and humoral immune responses to the antigenic challenge by sheep red blood cells were performed.Moreover, the ability of peripheral blood lymphocytes to form radial segmentation（RS） of their nuclei was analyzed.Body weight and relative weight of spleen, liver, and bursa of Fabricius were recorded.Results： Results showed that mean heterophile/lymphocyte ratio increased in the SBR groups compared to the control group and the blood of the chickens showed lymphocytic depletion. The results also demonstrated that the relative weight of bursa of Fabricius and spleen in groups fed with SBR significantly decreased compared to the control group. This study also showed that the addition of SBR significantly inhibited the formation of RS of nuclei compared to some cytotoxic substances.Conclusion： We found that SBR supplementation should be carefully evaluated when given to poultry. The excess intake of SBR supplementation may cause immunologic inhibition and may negatively affect the development of immune organs. SBR has inhibited the formation of radial segmentation nuclei showing antimetastatic properties and also the phagocytosis of chicken heterophils.

Toxic Effects of Phthalates on Ocean Algae

This article discusses the interaction of phthalates and ocean algae based on the standard appraisal method of chemical medicine for algae toxicity. Through the experiments on the toxic effects of dimethyl (o-) phthalate (DMP), diethyl (o-) phthalate (DEP), dibutyl (o-) phthalate (DBP) on ocean algae, the 50 % lethal concentration of the three substances in 48 h and 96 h for plaeodectylum tricornutum, platymonas sp, isochrysis galbana, and skeletonema costatum is obtained. Tolerance limits of the above ocean algae of DMP, DEP, and DBP are discussed.

Toxic effect of dinoflagellate Alexandrium species on Cladocera Moina mongolica Daday

The main objective of this study was to investigate toxic effects of the dinoflagellate Alexandrium species, on cladocera Moina mongolica in the laboratory. Ten strains of Alexandrium species, including Alexandrium tamarense （AT-6, ATHK, ATCI02, ATCI03 and AT5-1）, A. catenella （ACDH）, A. affine （AC-1 and AS-1）, A. lusitanicum and A A. tamarense （ATHK, ATCI02 and AT5-1） and A minutum were tested. The results showed that affine （AC-1 and AS-1）, but not A. tamarense （AT-6 and ATCI02）, A. catenella （ACDH）, A. lusitanicum and A. minutum had significantly negative effects on the survival of M. mongoliea; when exposed to these ten strains of Alexandrium species in densities of 3 000 cells/cm^3 for 7 d, respecyively. M. mongolica could feed on A. tamarense （AT-6, ATHK, ATCI02, ATCI03 and AT5-1）, A. eatenella, A. lusitanieum and A. minutum, but exhibited little or no grazing on A. affine （AC-1 and AS-1）, based on the changes in gut pigment af- ter exposure to alga for 1 and 12 h. A. affine AC-1, which had the strongest toxicity on the survival of M. mongolica, was chosen to further study the negative effects on M. mongolica. The results showed that the effect of A. affine AC-1 on the survival of M. mongolica was density-dependent, and its lethal effects on one-day, two-day and three-day old M. mongolica were exacerbated with increasing age; The whole algal culture, re-suspended algal cells, cell fragments and cell contents all had adverse impacts on the survival of M. mongolica. Moreover, both juvenile numbers and life-span time of M. mongolica were decreased significantly when they were cultured in A. affine AC-1 of 10 and 50 cells/cm^3, combined with 3×10^6 cells/cm^3 of Chlorella spp., respectively. As a non-PSP producer, A. affine may produce other toxins, responsible for the strong negative effects on M. mongolica.

Experimental Podophyllotoxin (Bajiaolian) Poisoning:Ⅲ. Biochemical Bases for Toxic Effects

The biochemical mechanism underlying the toxicity of podophyllotoxin is investigated.Previous studies from our laboratories suggested that hepatocytes were extremely sensitive to the toxicity of podophyllotoxin and a disruption of protein synthesis was suspected.Dose-response and time-course studies on the effects of podophyllotoxin on protein, RNA,and DNA syniheses on hepatocellular cultures were made. Inhibitions of protein, RNA,and DNA syntheses were demonstrated, and a direct correlated dose-response relationshipon such effects was also evident. Inhibition of protein synthesis appeared to be a direet toxic effect of podophyllotoxin and occurred independently from that of RNA. The reduction of DNA synthesis was reflected by a reduction of H3-thymidine incorporation,which is believed to be the consequence of inhibition on the mitotic activity by podophyllotoxin