Long-term effects of commercial and congeneric polychlorinated biphenyls on ethane production and malondialdehyde levels,indicators of in vivo lipid peroxidation

Ethane exhalation was increased in male Sprague-Dawley rats following a single intraperitoneal (IP) injection of Aroclor 1254 (500 mg/kg). In the first 2 weeks following Aroclor 1254 treatment, the increase in ethane exhalation was due to an inhibition of metabolism of endogenous ethane rather than to an increase in ethane production. In weeks 3 and 4 following Aroclor 1254 administration, metabolic clearance of ethane returned to and exceeded control levels, while ethane production increased to approximately twice the control rates (day 30). The HPLC determination of in situ hepatic malondialdehyde levels revealed a 2-fold increase in malondialdehyde content on day 30 following the Aroclor 1254 injection. Further, parallel increases in in situ malondialdehyde levels and ethane production rates were also found 30 days following a single IP injection of 3,3,4,4-tetrachlorobiphenyl, 2,3,4,4,5-pentachlorobiphenyl and 2,2,4,4,5,5-hexachlorobiphenyl (300 mol/kg). These effects were not reflected in increased diene conjugation. Redox state of the liver was largely unaffected, as evidenced by the relative concentrations of reduced and oxidized NADPH. However, minor changes in reduced and oxidized glutathione were noted.     

Toxicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)

In summary, the toxicity of TCDD has been comprehensively examined in multiple acute, subchronic, and chronic studies. Acute toxicity studies have shown marked species differences, with up to a 10,000-fold difference between the single oral LD50 dose for the guinea pig and hamster. TCDD is capable of causing an acnegenic response in man and a similar skin response in certain animals. It is also a potent inducer of microsomal enzymes in some but not all species. A dose-related suppression of cell-mediated immunity has been observed at higher dose levels in laboratory animals but not in humans manifesting TCDD-induced acnegenic response. TCDD causes a dose-related teratogenic response in mice, with the no-adverse-effect level of 0.1 micrograms TCDD/kg/day. In rats, TCDD causes embryo- and fetotoxicity above the no-adverse-effect level of 0.03-0.125 micrograms/kg/day. Dose-related reproductive effects have also been noted in monkeys at doses that elicit maternal toxicity, and additional long-term studies are presently underway. A multigeneration reproduction study as well as a lifetime chronic toxicity study have been completed with TCDD in rats; in both studies, the no-adverse-effect level was found to be 0.001 microgram TCDD/kg/day. Numerous mutagenic studies have been performed using in vitro plant and microbial test systems as well as in vivo tests in mammals and man. A mutagenic response was noted in a few of the vitro test systems, but there are no definitive in vivo correlates of TCDD mutagenicity in higher mammals or man. TCDD has been studied for carcinogenic potential in rats and mice. There is good correlation of the results, with a carcinogenic response noted in both species only after long-term ingestion of higher dose levels that induce toxicity. No carcinogenic response occurred at continuous dose levels of 0.001-0.0014 micrograms/kg/day in rats and 0.001-0.03 micrograms/kg/day in mice. Data presently available are more supportive of a nongenetic (?promotor) rather than a genetic mechanism of carcinogenesis. The most recent research, some of which is still underway, indicates that the biologic uptake and toxicity of TCDD may be significantly decreased if the TCDD is adsorbed onto carbon or soil particles. This information is helpful in hazard assessment of exposure to TCDD.     

Lipid peroxidation in isolated rat hepatocytes measured by ethane and n-pentane formation

Isolated rat hepatocytes (1×10⁷ cells/ml) were aerobically incubated in Eagle's Minimum Essential Medium which contained 2.0% albumin. As potential parameters of lipid peroxidation ethane and n-pentane formed were measured in samples obtained from the gas phase above the incubation mixture. 15–30 nmol ethane or n-pentane were produced by 10⁷ hepatocytes within 90 min. Carbon tetrachloride (CCl₄) or ADP-complexed ferrous ions stimulated ethane and n-pentane formation considerably, depending on the concentrations of the compounds. With CCl₄ 10⁷ cells formed max 180 nmol ethane and 140 nmol n-pentane within 90 min incubation, whereas with Fe(II) max 130 nmol ethane and 220 nmol n-pentane could be detected.When n-pentane was added to the gas phase above the incubation mixture containing either medium or medium plus hepatocytes its amount decreased by 30% within the first 5 min of incubation. However, afterwards only minor amounts of n-pentane disappeared, even in the presence of hepatocytes. This indicates that n-pentane equilibrates with the cell suspension under the conditions used.Cell viability, as determined by the release of lactate dehydrogenase into the medium and by the uptake of trypan blue by the cells, and the recovery of the cells decreased only in presence of relatively high concentrations of CCl₄, or Fe(II) respectively. However, a maximal effect on ethane and n-pentane formation was reached already with lower concentration.The results have been presented in part during the 22nd Spring Meeting of the Deutsche Pharmakologische Gesellschaft [de Ruiter N, Ottenwälder H (1981) Naunyn-Schmiedebergs Arch Pharmacol (Suppl) 316: R 20]     

Expiration of ethane in rats under variously elevated inspiratory O2-concentrations

Expired ethane is regarded as a noninvasive indicator of lipid peroxidation. As a model of oxidative stress we have investigated in male Wistar rats (body wt. 309 ± 15 g) the effects of various levels of elevated inspiratory oxygen concentrations on the expiration rate of ethane. After 4 days under 21 vol% O₂ (basic condition) the rats were exposed for 6 or 5 days to 40, 60 or 80 vol% O₂ over 8 or 23 h/day. The variously O₂-enriched air was conducted through the cages and expired ethane adsorbed onto charcoal was thermo-desorbed and measured by gas chromatography. Basic ethane expiration was 3.1 ± 0.8 pmol/100 g body wt. per min. At 40 vol% O₂ over 8 or 23 h/day no increase or a maximum average 47% increase (P < 0.01) in ethane expiration occurred on day 4; 60 vol% O₂ over 8 or 23 h/day led to a corresponding increase of 56 or 87% (P < 0.05 or P < 0.01) on day 3; 80 vol% O₂ over 8 or 23 h/day led to a corresponding increase of 81 or 66% (P < 0.01) on days 3 or 2. Our results indicate that with up to 60 vol% O₂ a temporary increase in lipid peroxidation occurs in a dose dependent manner. However, at 80 vol% O₂ no further increase in the maximum ethane expiration occurred. The latter finding and the finding of only transient increase in ethane expiration in probably due to antioxidative counteraction. Received: 7 October 1997 / Accepted: 3 November 1997     

镉所致肾损害与脂质过氧化的实验

每天以２ｍｇ／ｋｇ氯化镉生理盐水溶液给大鼠腹腔注射１５天，结果显示：氯化镉可引起肾功能的改变和脂质过氧化指标ＭＤＡ的升高及ＳＯＤ的下降，说明镉可诱发肾脏的脂质过氧化。亚细胞组分分析表明镉诱导的脂质过氧化主要发生在线粒体及微粒体中。比较脂质过氧化与肾损害出现的时间，可见染镉动物肾皮质及亚细胞组分ＭＤＡ的升高及ＳＯＤ的下降的时间均晚于肾功能异常。可以认为肾脏脂质过氧化并非镉引起肾损害的直接原因     

Mechanism of enhanced lipid peroxidation in the liver of Long-Evans cinnamon (LEC) rats

The Long-Evans Cinnamon (LEC) rat is a mutant strain of rats that accumulate copper (Cu) in the liver in much the same way as individuals who suffer from Wilson's disease (WD) and has been suggested as a model for this disease. Lipid peroxidation (LPO) is considered to be involved in the toxic action of Cu in the livers of LEC rats. We investigated the mechanism of LPO in the livers of LEC rats showing apparent signs of hepatitis. Several-fold higher LPO levels were observed in post-mitochondrial supernatant (S-9) fraction of livers from hepatitic LEC rats than in those from Wistar rats. To mimic living cells, we introduced NADPH-generating system (NADPH-gs) into the S-9 incubation system. Thus was ensured a constant supply of NADPH to vital enzymes that may be directly or indirectly involved in the generation and/or elimination of reactive oxygen species (ROSs), such as glutathione reductase (GSSG-R), which require NADPH for their reactions. The levels of LPO in liver S-9 from hepatitic LEC rats were further increased by incubating liver S-9 at 37 °C in the presence of NADPH-gs. This increase was inhibited by EDTA, butylated hydroxytoluene (BHT), and catalase (CAT), suggesting that some metal, most likely the accumulated Cu, and ROSs derived from hydrogen peroxide (H₂O₂) are involved in the increased levels of LPO in the livers of hepatitic LEC rats. The requirement of NADPH-gs for enhanced LPO in the livers of hepatitic LEC rats indicates the consumption of NADPH during reactions leading to LPO. It is known that H₂O₂, and consequently hydroxyl radical are generated during Cu–catalyzed glutathione (GSH) oxidation. The cyclic regeneration of GSH from GSSG by NADPH-dependent GSSG-R in the presence of NADPH-gs may cause sustained generation of hydroxyl radical in the presence of excess free Cu. The generation of H₂O₂ in S-9 fraction of livers from hepatitic LEC rats was observed to be significantly higher than that in S-9 fraction of livers from non-hepatitic LEC rats and Wistar rats. Moreover, in addition to the reported decrease in glutathione peroxidase (GPX) activity, we found that CAT activity was markedly decreased in LEC rats with hepatitis. The increased generation of H₂O₂ with reduced activities of GPX and CAT may result in cellular accumulation of H₂O₂ in the liver of hepatitic LEC rats. Taken altogether, it is suggested that the accumulated H₂O₂ undergoes the Fenton-type reaction with also accumulated free Cu, thus generating hydroxyl radical in the livers of hepatitic LEC rats and increasing LPO levels in these animals. Received: 20 April 1999 / Accepted: 2 September 1999     

氯丙烯亚慢性中毒大鼠血清脂质过氧化的时效关系

目的研究氯丙烯(AC)亚慢性中毒大鼠血清脂质过氧化的改变是否存在时间效应关系,探讨其中毒性神经病发病机制。方法选用90只Wistar雄性大鼠随机分为对照组(n=50)和染毒组(n=40),染毒组大鼠以200 mg/kg剂量AC经口灌胃,每周3次,分别在染毒第3、6、9和12周随机从对照组和染毒组取大鼠10只,用生物化学方法测定染毒组与相应时间对照组大鼠血清中丙二醛(MDA)、谷胱甘肽(GSH)含量、抗活性氧能力(anti-ROS)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、超氧化物岐化酶(SOD)和总抗氧化能力(T-AOC)活力等指标。结果随染毒时间的延长和步态评分的增加,MDA呈进行性升高趋势;anti-ROS、GSH、GSH-Px、CAT、SOD、T-AOC呈下降趋势。MDA从染毒第3周和步态评分2分开始升高,与对照组相比差异有统计学意义(P<0.05)。结论AC亚慢性染毒可引起大鼠血清发生脂质过氧化,并且存在明显的时间效应关系,脂质过氧化可能是AC诱导的神经毒性的发病机制之一;MDA改变的最早、最为敏感,可为AC中毒的早期诊断提供了依据。     

Induction of lipid peroxidation in human fibroblasts by the antioxidant propyl gallate in combination with copper(II)

The antioxidant propyl gallate (PG) induced lipid peroxidation in combination with non-toxic Cu(II) concentrations in human fibroblasts. This was measured by the thiobarbituric acid assay (TBA assay) and by detection of accumulating fluorescent products after a 1-h treatment of cells with CuCl₂/PG at concentrations higher than 0.125 mM. PG alone led to a significant reduction of thiobarbituric acid-reactive substances (TBARS) demonstrating its antioxidative properties. Time course studies of lipid peroxidation by PG/Cu(II) showed that formation of TBARS was preceded by a lag phase of 60 min. Thereafter, the TBARS value increased rapidly for 1 h and then reached a constant maximum or slightly decreased. The induction of lipid peroxidation by PG/Cu(II) is probably due to the formation of reactive species like reactive oxygen species (ROS), Cu(I) and semiquinone radicals which are able to participate in initiation and propagation of lipid peroxidation. Combination effects of PG/Cu(II) were demonstrated also on inhibition of membrane-bound succinate dehydrogenase. Cytosolic esterases were affected only slightly. The greater susceptibility of membrane-bound enzymes is in accordance with the lipid peroxidation-inducing effects of PG/Cu(II).     

Effects of spirotetramat on the acute toxicity,oxidative stress,and lipid peroxidation in Chinese toad (Bufo bufo gargarizans) tadpoles

The aim of this work was to evaluate the potential effects of antioxidant and lipid peroxidation parameters as indicators of exposure to spirotetramat and effects of acute toxicity in the Chinese toad Bufo bufo gargarizans. The results of an acute toxicity test showed that the 72 and 96 h median lethal concentrations (LC₅₀) of spirotetramat for tadpoles were 6.98 and 6.45 mg/L, respectively. It indicated that the spirotetramat was moderate toxicity to Chinese toad tadpoles. In a sub-lethal toxicity test, the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) contents were determined after exposure to 0.03, 0.06, 0.13, 0.65, and 3.23 mg/L for 4, 15, and 30 days. SOD activity significantly in all experimental groups except the highest concentration group increased on day 4 but decreased on days 15 compared with that of the acetone control (P < 0.05). The most sensitive parameters was GSH-Px activity, which significantly increased on day 4, but was inhibited and decreased after prolonged exposure for 15 and 30 days except the lowest concentration treatment group (P < 0.05). The MDA content significantly decreased on day 30 (P < 0.05). During the entire experimental period, sub-lethal doses spirotetramat caused oxidative stress and lipid peroxidation in B. gargarizans tadpoles. These results indicate that sub-lethal even non-lethal spirotetramat are potentially toxic to amphibians. The information presented in this study will be helpful for understanding oxidative stress induced by spirotetramat in aquatic organisms.     

不同价态锰对不同月龄大鼠脂质过氧化的影响

目的　研究不同价态锰染毒后对大鼠脑、肝和心肌内脂质过氧化(MDA)和超氧化物歧化酶(SOD)活力的影响。方法　大鼠经腹腔分别注射氯化锰(MnCl2 ·4H2 O ,Mn2 )和醋酸锰(C6 H9O6 Mn·2H2 O ,Mn3 ) ,按6mg kg剂量连续染毒1个月后,测定脑、肝和心肌组织中MDA含量和SOD活力。结果　(1)经Mn2 染毒后大鼠脑组织MDA含量与对照组相比,差异有显著性(P <0 0 5 ) ,而Mn3 染毒后只有18月龄大鼠脑组织MDA含量显著高于对照组(P <0 0 5 ) ;在肝组织MDA含量,Mn2 组与对照组相比,差异有显著性(P <0 0 5 )。(2 )经Mn2 、Mn3 染毒后18月龄和4月龄大鼠脑组织SOD活力显著低于对照组(P <0 0 5 ) ;经Mn2 染毒后,18月龄和4月龄大鼠肝SOD活力明显低于对照组(P <0 0 5 ) ;经Mn3 染毒后,18月龄大鼠肝SOD活力显著低于对照组(P <0 0 5 )。(3 )心肌组织MDA含量,SOD活力与对照组相比,差异均无显著性。结论　不同价态、不同剂量锰染毒不同月龄大鼠对其不同组织MDA含量和SOD活力的影响是不同的。     

黄芪对D-半乳糖衰老大鼠脂质过氧化及红细胞免疫功能的影响

目的 探讨黄芪对D-半乳糖衰老大鼠脂质过氧化及红细胞免疫功能的影响.方法 30只Wister大鼠分为正常对照组、D-半乳糖模型组和黄芪给药组,测定血清丙二醛(MDA)、心肌组织脂褐素(LPF)的含量、红细胞C3b受体花环率(RBC-C3bRR)、红细胞免疫复合物花环率(RBC- ICR).结果 与正常对照组相比较,D-半乳糖模型组大鼠体内血清MDA、心肌LPF含量和RBC-ICR升高,RBC-C3bRR降低(P＜0.01);而给予黄芪后,D-半乳糖模型大鼠体内血清MDA和心肌LPF含量降低,RBC-C3bRR升高、RBC-ICR降低(P＜0.01).结论 黄芪可以通过降低脂质过氧化水平,增强红细胞免疫功能而发挥抗衰老作用.     

脂质过氧化法测定动物体内自由基的含量

目的建立一种可以测定动物组织中自由基含量的化学方法。方法取老龄小鼠心、肝、脾、肺、肾、脑、肌肉的组织样品,以及Beagle犬口服超氧化物歧化酶(SOD)溶液以后不同时间的血浆样品,用脂质过氧化法测定其中自由基的含量。结果标准曲线回归方程为:A=0.0285C-0.0443(r=0.9970),线性范围为8.27~41.35 nmol.ml-1,日内和日间精密度RSD均低于8%,高、中、低浓度样品的加样回收率分别为100.68%、99.66%、97.95%。测得小鼠体内各组织的自由基含量和分布与文献报道的相符合,而Beagle犬口服SOD溶液后血浆中的自由基含量逐渐降低,并于2.5 h出现最低值。结论脂质过氧化法测定动物体内自由基的含量,线性和重复性均好,加样回收率高,仪器简单,试剂价廉,操作方便。     

Correlation between lipid peroxidation and morphological manifestation of paraquat-induced lung injury in rats

Biochemical and morphological studies of rat lung were performed to determine the role of lipid peroxidation in the in vivo lung toxicity of paraquat. Two injections of 20 mg/kg paraquat were administered intraperitoneally every other day. While notable epithelial damage in the lungs was observed on the day after the second paraquat injection and progressed through the 5th day, the concentration of lipid peroxides in the rat lungs did not increase by the 3rd day after the injection. The lipid peroxide concentrations increased after the 5th day post-injection, and reached the maximum concentrations on the 7th day, when the damaged alveolar surface had been mostly repaired by regenerative pneumocytes. On the other hand, the delayed increase of lung lipid peroxides in paraquattreated rats paralleled the increased number of macrophages in the lung, which reached maximum numbers on the 7th day. Glutathione peroxidase activity in the lungs also increased with a similar time course. Macrophages from the lungs contained a large amount of engulfed degradation products and cellular debris, and immunohistochemical study showed high glutathione peroxidase content on the 5th and 7th days. These results suggest that lipid peroxidation is a relatively late event in the in vivo paraquat-treated lung and that the delayed increase of lipid peroxides in the lungs occurs from the phagocytic activities of macrophages rather than from toxic cell injury.     

Determination of alkanes in breath to monitor lipid peroxidation in the presence of volatile toxicants and metabolites

Determination of alkanes in breath of laboratory animals and humans has become a standard-method for monitoring lipid peroxidation in vivo. Isothermal gas chromatography on Porasil C enables sensitive, rapid and repetitive determination of all C₂-C₅-hydrocarbons in breath. Volatile toxicants and metabolites, which would coelute with the alkanes of later injected samples, are deviated by using a precolumn. An automatic switching unit controls withdrawal and injection of samples and backflush of the precolumn in a repetitive manner at fixed intervals. This increases accuracy and sensitivity of analysis and enables virtually unattended operation. The system has been applied for a study on the oxygen-dependance of CCl₄-metabolism in the rat.     

混合蔬菜汁对四氯化碳染毒大鼠脂质过氧化和转氨酶活性的影响

目的　以四氯化碳 (CCl4 )染毒大鼠为肝损伤动物模型 ,观察了胡萝卜、西红柿、甘蓝、莴苣、芹菜、洋葱、茄子、菠菜等 8种蔬菜的混合菜汁对大鼠脂质过氧化和转氨酶活性的影响 ,并探讨其可能机制。方法　将 110只大鼠随机分为 5组 :对照组、CCl4 组、CCl4 +提前给予混合蔬菜汁组、CCl4 + 10 0 %混合蔬菜汁组、CCl4 + 5 0 %混合蔬菜汁组。CCl4 按0 3 5ml kg 1次性腹腔注射 ,混合蔬菜汁按 1ml 10 0g体重灌胃。分别于染毒后第 1天、第 2天、第 7天将各组大鼠随机处死 6只 ,测定血清丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST)活性 ,血清脂质过氧化 (LPO)水平 ,血清铜蓝蛋白 (CP)含量 ,血清、肝匀浆超氧化物歧化酶 (SOD)活性 ,血清、肝匀浆过氧化氢酶 (CAT)活性。结果　各染毒组肝 体比值增加 ,血清ALT、AST活性增高 ,LPO水平升高 ,各混合蔬菜汁组血清AST、ALT活性均低于CCl4 组 ,以 5 0 %组血清AST、ALT活性最低。结论　在染毒同时给予 5 0 %混合蔬菜汁 ,对CCl4 引起LPO有明显的拮抗作用 ,可能与其能清除·CCl3有关。     

Low pH does not modulate antioxidant status of diphenyl ditelluride but exacerbates Fe (II)-induced lipid peroxidation in liver preparation

The relationship of acidosis and lipid peroxidation in liver homogenate was studied and the effect of pH on the antioxidant potential of diphenyl ditelluride is reported. Low pH increased the rate of lipid peroxidation both in the absence and presence of Fe (II), while diphenyl ditelluride (DPDT) inhibited the rate of lipid peroxidation in a concentration-dependent manner at all studied pH values. However, the change in pH did not alter the antioxidant activity of the compound. This study shows acidosis catalyzed oxidative stress in liver homogenate and the antioxidant potential of diphenyl ditelluride.     

Metabolism and distribution of [14C]glucose in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Male Sprague-Dawley rats were given a single, usually lethal, dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 125 micrograms/kg ip in corn oil), or vehicle alone. Twenty-four hours after ip administration of TCDD the animals received an ip injection of 14C-labeled glucose, and the time course and amount of exhalation of 14CO2 were monitored for 8 h continuously and once daily for 20 min for the subsequent 5 d. TCDD treatment reduced the amount of 14CO2 exhaled within 8 h after the injection of [14C]glucose by 33%, as compared to pair-fed controls. Blood levels of radioactivity were affected by TCDD accordingly. No particular organ appeared to act as a sink for the radioactivity not exhaled during these 8 h by the treated animals. TCDD (125 micrograms/kg) induced significant changes in the disposition of radioactivity in heart and brown adipose tissue between 25 and 125 min after the iv injection of [14C]glucose. The areas under the curve of [14C]glucose-derived radioactivity were the same after either iv or ip injection in the blood of TCDD-treated rats, allowing a direct comparison of experiments with iv or ip injection of [14C]glucose. The half-lives of radioactivity in the exhaled air and in feces of treated animals were greatly elevated during the 5 d following administration of [14C]glucose. These results indicate that TCDD induces in rats, within 24 h after dosing, alterations in the metabolism of glucose that preceded changes in insulin homeostasis, because hypoglycemia and hypoinsulinemia in rats do not occur until about a week after TCDD treatment. Since overt signs of acute toxicity (reduced feed intake and body weight loss) are also not noticeable until several days after a lethal dose of TCDD, it is probable that this earlier disturbance of glucose metabolism is part of the biological changes that result in wasting away and eventually in death.     

Changes in food intake and food selection in rats after 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on food selection were studied in TCDD-resistant Han/Wistar and TCDD-sensitive Long-Evans rats and their crosses. The rats were offered a selection diet consisting of chocolate, cheese, and chow, and TCDD was given at the same time or 4 or 16 days later. TCDD persistently reduced the chocolate intake. When the selection diet was started at the time of or less than 11 h after TCDD exposure, TCDD almost completely prevented the intake of chocolate and also cheese in all strains already on the first day, while controls started to consume large amounts of both foods. This may be due to conditioned taste aversion. The effect on food selection with familiar foods seemed to reduce fat intake, while protein and carbohydrate intakes were more variable. There were no major strain differences in the chocolate intake inhibition despite a 1000-fold sensitivity difference in TCDD lethality.     

Combined effects of okadaic acid and cadmium on lipid peroxidation and DNA bases modifications (m5dC and 8-(OH)-dG) in Caco-2 cells

Okadaic acid (OA) is a marine toxin, a tumour promoter and an inducer of apoptosis. It mainly inhibits protein-phosphatases, protein synthesis and enhances lipid peroxidation. Cadmium (Cd) is known to be carcinogenic in animals and humans (group 1 according to the International Agency for Research on Cancer (IARC) classification). Cd also induces oxidative stress in living organisms. Since they are sometimes found simultaneously in mussels, we have evaluated in the present investigation, the lipid peroxidation, as malondialdehyde (MDA) production, in the variation of the ratios of 8-(OH)-dG/10⁵dG and m⁵dC/ (dC + m⁵dC) induced by OA and/or Cd in Caco-2 cells. When cells were treated exclusively by OA (15 ng/ml) or Cd (0.625 and 5μg/ml) for 24 h, protein synthesis was inhibited (by 42 ± 5%, 18 ± 13%, and 90 ± 4% respectively) while MDA production was 2235 ± 129, 1710 ± 20, and 11496 ± 1624 pmol/mg protein respectively. In addition, each toxicant induced modified bases in DNA; increases in oxidised bases and methylated dC. The combination of OA and cadmium was more cytotoxic and caused more DNA base modifications; the ratio m⁵dC/(m⁵dC+dC) was increased from 3 ± 0.15 to 9 ± 0.15 and the ratio 8-(OH)-dG/10⁵ dG also (from 36 ± 2 to 76 ± 6). The combination of OA and Cd also increased the level of MDA (16874 ± 2189 pmole/mg protein). The present results strongly suggest that DNA damage resulting from the oxidative stress induced by these two toxicants may significantly contribute to increasing their carcinogenicity via epigenetic processes. Received: 28 September 1999 / Accepted: 10 January 2000     

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and fasting on body weight and lipid parameters in rats

This study compared the effect of fasting (feed deprivation) and the effect of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on body weight and on key lipid parameters. The time-course study indicated a statistically significant (p less than 0.05) body weight loss in the TCDD-exposed rats 5 days after the oral administration of corn oil with TCDD (60 micrograms/kg body wt). Animals demonstrated a 10% body weight decrease either 1 week after this TCDD administration or after 72 hr of fasting. Marked increases in serum triglyceride and cholesterol were observed only in the TCDD-exposed rats, but not in the 0- or 72-hr fasted control rats. These results indicated that some body weight loss and decreased feed consumption occurred after TCDD exposure, but that the metabolic response, with respect to serum lipid metabolism, was not that of a control rat that had lost a similar amount of body weight due solely to fasting.