Cell ATP level of Saccharomyces cerevisiae sensitively responds to culture growth and drug-inflicted variations in membrane integrity and PDR pump activity.

Cellular ATP level in Saccharomyces cerevisiae was measured during culture growth of strain US50-18C overproducing all major PDR pumps and its isogenic mutants variously deleted in these pumps. It was found to be inversely proportional to the intensity of cell metabolism during different growth phases and to the activity of PDR pumps, which are thus among major ATP consumers in the cells. The ATP level was increased when membrane integrity was affected by 0.5% butanol, and further increased by compound 23.1, a semisynthetic phenol lipid derivative that acts as inhibitor of Pdr5p and Snq2p pumps. The magnitude of increase in cell ATP caused by inhibition of Pdr5p pump by compound 23.1 and the Pdr5p pump inhibitor FK506 used for comparison reflects the activity and hence the energy demand of the pump. The rise in cell ATP caused by different PDR pump inhibitors can be thus used as an indicator of pump activity and the potency of the inhibitor.

Cell-protective and antioxidant activity of two groups of synthetic amphiphilic compounds--phenolics and amine N-oxides.

Two classes of newly synthesized amphiphilic compounds, phenolic antioxidants ("phenolics") and N-oxides exert in vivo antioxidant effects on live S. cerevisiae cells. Both groups have low toxicity, phenolics being more toxic than N-oxides and compounds with a longer alkyl chain having higher toxicity than those with a shorter alkyl chain. Phenolic antioxidants protect yeast cells exposed to the superoxide producer paraquat and peroxyl generator tert-butylhydroperoxide better than N-oxides at 3-fold higher concentration. Both types of antioxidants enhance the survival of pro-oxidant-exposed cells of S. cerevisiae mutants deficient in cytosolic and/or mitochondrial superoxide dismutase and could be good compounds which mimic the role of superoxide dismutases. The results of measurement of antioxidant activity in an in vitro chemiluminescence test differ from the results obtained in vivo with S. cerevisiae superoxide dismutase mutants. In contrast to their action on live cells, phenolics are less effective than N-oxides in preventing lipid peroxidation of an emulsion of lipids isolated from S. cerevisiae membranes.

Protective role of mitochondrial superoxide dismutase against high osmolarity, heat and metalloid stress in saccharomyces cerevisiae.

Superoxide dismutases, both cytosolic Cu, Zn-SOD encoded by SOD1 and mitochondrial Mn-SOD encoded by SOD2, serve Saccharomyces cerevisiae cells for defense against the superoxide radical but the phenotypes of sod1A and sod2delta mutant strains are different. Compared with the parent strain and the sod1delta mutant, the sod2delta mutant shows a much more severe growth defect at elevated salt concentrations, which is partially rescued by 2 mmol/L glutathione. The growth of all three strains is reduced at 37 degrees C, the sod2delta showing the highest sensitivity, especially when cultured in air. Addition of 1 mmol/L glutathione to the medium restores aerobic growth of the sod1delta mutant but has only a minor effect on the growth of the sod2delta strain at 37 degrees C. The sod2delta strain is also sensitive to AsIIl and AsV and its sensitivity is much more pronounced under aerobic conditions. These results suggest that, unlike the Sodlp protein, whose major role is oxidative stress defense, Sod2p also plays a role in protecting S. cerevisiae cells against other stresses--high osmolarity, heat and metalloid stress.

Assaying the antioxidant and radical scavenging properties of aliphatic mono- and di-N-oxides in superoxide dismutase-deficient yeast and in a chemiluminescence test.

The antioxidative action of amphiphilic mono-(alkanoylamino) ethyldimethylamine-N-oxides (EDA), di-N-oxides 1,1-bis {[2-(N,N-dimethylamino)ethyl]amido}alkane-di-N-oxides (MEDA) and 1,1-bis {[3-(N,N-dimethylamino)propyl]amido}alkane-di-N-oxides (MPDA) with a 12- and 14-membered acyl chain against tert-butylhydroperoxide (TBHP)-produced peroxyl and paraquat (PQ)-generated superoxide radicals was determined in superoxide dismutase-deficient mutants of Saccharomyces cerevisiae, and, in parallel, in a chemical assay based on chemiluminescence changes caused in a luminol system by peroxyl radicals generated from the azo-compound 2,2'-azobis(2-amidinopropane dihydrochloride) (AAPH). At 30 micromol/L, the shorter-chain compounds did not affect strain survival while longer-chain ones, in some cases, lowered the survival of sod2 and sod1 sod2 cells. Whether nontoxic or medium-toxic, all N-oxides protected the sod strains against the toxic effect of PQ and TBHP, the protection being stronger with the di-N-oxides. The survival was lowered only by 14-MPDA in the TBHP-exposed sod2 mutant. Membrane lipids isolated from all strains were protected against TBHP-induced peroxidation by both mono- and di-N-oxides, the protection being dependent on the alkyl chain length. Mono-N-oxides were again less active than di-N-oxides with the same alkyl chains, the antiperoxidative activity being also dependent on lipids isolated from the individual mutants. In the chemiluminescence assay, the IC50 value of the N-oxides for scavenging of radicals generated from AAPH generally decreased (i.e. the scavenging efficiency increased) with increasing chain length and was the highest in MEDA.

Amphiphilic amine-N-oxides with aliphatic alkyl chain act as efficient superoxide dismutase mimics, antioxidants and lipid peroxidation blockers in yeast.

Amphiphilic 3-(alkanoylamino)propyldimethylamine-N-oxides with different length of the alkyl chain, i.e. different hydrophilic-lipophilic balance, act in micromolar concentrations as SOD mimics by lifting the inhibition of aerobic growth caused by SOD deletions in Saccharomyces cerevisiae. They also enhance the survival of sod mutants of S. cerevisiae exposed to the hydrophilic superoxide-generating prooxidant paraquat and the amphiphilic hydroperoxide-producing tert-butylhydroperoxide (TBHP), and largely prevent TBHP-induced peroxidation of isolated yeast plasma membrane lipids. Unlike the SOD-mimicking effect, the magnitude of these effects depends on the alkyl chain length of the amine-N-oxides, which incorporate into S. cerevisiae membranes, causing fluidity changes in both the hydrophilic surface part of the membrane and the membrane lipid matrix. Unlike wild-type strains, the membranes of sod mutants were found to contain polyunsaturated fatty acids; the sensitivity of the mutants to lipophilic pro-oxidants was found to increase with increasing content of these acids. sod mutants are useful in assessing pro- and antioxidant properties of different compounds.

Reductions in physical pain predict lower risk of relapse following alcohol treatment.

OBJECTIVE: Physical pain is considered a potential predictor of relapse in alcohol-dependent individuals after treatment. The aim of this study was to evaluate whether reductions in pain level during the follow-up period after treatment were associated with lower relapse risk. METHOD: A sample of 366 participants was recruited from alcohol treatment centers in Warsaw, Poland. At baseline, information was obtained about pain level, demographics, childhood abuse, impulsivity, depressive symptoms, severity of alcohol and sleep problems. After finishing the alcohol treatment program, patients were followed for 12 months and alcohol drinking (relapse) as well as pain severity were evaluated. RESULTS: In the followed-up group, 29.5% of patients confirmed that they drank any alcohol during past 4 weeks. Comparing follow-up to baseline pain, 48.6% of subjects reported an increased severity of pain, 28.8% reported the same level of pain, 22.6% reported decreased level of pain. There was a significant association between the decrease in level of pain and the lower risk of relapse. Other factors associated with relapse during 4 weeks prior to the follow-up were baseline severity of depressive symptoms, low baseline social support and number of drinking days during 4 weeks prior to entering treatment. In multivariate analysis, a decrease in pain level was associated with a lower likelihood of relapse (OR=0.159; 95%CI:0.04-0.62; p=0.008) even when controlled for other factors associated with relapse. CONCLUSIONS: Decreases in pain level following treatment for alcohol dependence are associated with, and may contribute to, a lower risk of alcohol relapse.

Dietary cadmium decreases lipid peroxidation in the liver and kidneys of the bank vole (Clethrionomys glareolus).

The effect of elevated levels of dietary cadmium on lipid peroxidation in the liver and kidneys of a small rodent, the bank vole, was determined in the present study. Males and females, aged 1 month, were given diets containing 0.40 and 80 mg Cd per kg; liver and kidneys were removed for TBA-RS as well as iron, copper, zinc, cadmium and metallothionein analyses at the end of 6 weeks. Dietary Cd significantly decreased the TBA-RS level in the liver and kidneys of both sexes; however, this effect appeared to be dose-dependent only for the male liver. The changes in hepatic and renal TBA-RS paralleled closely those of tissue iron. Copper concentration decreased significantly only in the male liver, while hepatic and renal zinc were not influenced by dietary Cd. The concentrations of Cd and metallothionein in the liver and kidneys increased significantly in a dose-dependent fashion. Regression analysis confirmed that TBA-RS in both organs correlated closely with iron. The data suggest that dietary Cd decreases hepatic and renal lipid peroxidation indirectly, through lowering the tissue iron concentration.

Photoperiodic elevation of testicular zinc protects seminiferous tubules against fluoride toxicity in the bank vole (Clethrionomys glareolus).

Recent work has shown that a high fluoride (F) intake in rodents leads to histopathologic changes in the germinal epithelium of testes and to zinc deficiency in the testis and several other organs. The purpose of the present study was to determine whether an elecvation of testicular zinc concentration during fluoride exposure could protect the testes of bank vole from damage. The elevation of testicular zinc was achieved by exposing the bank voles to a long photoperiod (16 hr light/8 hr dark). The zinc concentration in the testes of bank voles kept under the long photoperiod was 38% higher than that in animals exposed to a moderate photoperiod (12 hr light/12 hr dark). Fluoride exposure (200 micrograms F/ml drinking water) during 4 months decreased additionally (p < 0.05) zinc concentration in the testes of bank voles kept under the moderate photoperiod. The same animals also exhibited histopathologic changes in the germinal epithelium. By contrast, these disturbances were not observed in animals maintained in the long photoperiod. This experiment suggests that an increase in testicular zinc due to a long photoperiod prevents seminiferous tubules from a damage induced by fluoride in bank voles. The protective effects of zinc (or a long photoperiod) did not appear to be related to a decrease in testicular fluoride accumulation or lipid peroxidation.

Monitoring the growth and stress responses of yeast cells by two-dimensional fluorescence spectroscopy: first results.

S. cerevisiae growth and responses to different treatments were monitored by two-dimensional fluorescence spectroscopy, which simultaneously detects the fluorescence of a number of cells' own fluorophores. Growth curves of cultures of free cells were measured by means of tryptophan fluorescence in nonfluorescent culture medium and a flow-through system at a suitable excitation/emission beam geometry. Fast responses of the cells to anaerobic-aerobic transition or addition of glucose, methanol or cyanide, which could not be measured in this system because of the time delay inherent in transporting the cells from the culture flask to the cuvette, were monitored with cells immobilized in alginate. The major fluorescence changes caused by these treatments belonged to NAD(P)H which is a good indicator of the redox state of the cells.

Role of strategic cysteine residues in oxidative damage to the yeast plasma membrane H(+)-ATPase caused by Fe- and Cu-containing Fenton reagents.

Damage caused to Saccharomyces cerevisiae SY4 plasma membrane H(+)-ATPase by Fe- and Cu-Fenton reagents was determined in secretory vesicles containing enzyme in which Cys residues were replaced singly or in pairs by Ala. Cys-221 situated in a beta-sheet domain between M2 and M3 segments, phosphorylation domain-located Cys-409 and Cys-532 situated at the ATP-binding site play a role in the inactivation. In the presence of all three residues the enzyme exhibited a certain basic inactivation, which did not change when Cys-532 was replaced with Ala. In mutants having intact Cys-532 but lacking one or both other cysteines, replacement of Cys-221 with Ala led to lower inactivation, suggesting that Cys-221 may serve as a target for metal-catalyzed oxidation and intact Cys-532 promotes this target role of Cys-221. In contrast, the absence of Cys-409 caused higher inactivation by Fe-Fenton. Cys-532 thus seems to serve as a target for Fe-Fenton, intact Cys-409 causing a conformational change that makes Cys-532 less accessible to oxidation. The mutant lacking both Cys-221 and Cys-409 is more sensitive to Fe-Fenton than to Cu-Fenton and the absence of both Cys residues thus seems to expose presumable extra Fe-binding sites. These data and those on protection by ATP, ADP, 1,4-dithiothreitol and deferrioxamine B point to complex interactions between individual parts of the enzyme molecule that determine its sensitivity towards Fenton reagents. ATPase fragmentation caused by the two reagents differed in that the Fe-Fenton reagent produced in Western blot "smears" whereas the Cu-Fenton reagent produced defined fragments.

Effect of antioxidants on Saccharomyces cerevisiae mutants deficient in superoxide dismutases.

S. cerevisiae strain delta sodl lacking Cu,Zn-superoxide dismutase and delta sodl delta sod2 mutant lacking both Cu,Zn-SOD and Mn-superoxide dismutase displayed strongly reduced aerobic growth on glucose, glycerol and lactate; delta sod2 deletion had no effect on aerobic growth on glucose and largely precluded growth on glycerol and lactate. The oxygen-induced growth defects and their alleviation by antioxidants depended on growth conditions, in particular on oxygen supply to cells. Under strong aeration, vitamins A and E had a low effect, 100 mumol/L quercetin alleviated the growth defects of all three mutants while beta-carotene had no growth-restoring effect. The superoxide producer paraquat inhibited the aerobic growth of all three mutants in a concentration-dependent manner. Low concentrations of antioxidants had no effect on paraquat toxicity while higher concentrations supported the toxic effect of the agent.

Spontaneous and radical-induced plasma membrane lipid peroxidation in differently oxidant-sensitive yeast species and its suppression by antioxidants.

Formation of thiobarbituric acid-reactive substances (TBRS; nmol/mg lipids) indicative of lipid peroxidation was measured in whole cells and in isolated plasma membrane lipids from three yeast species differing in oxidant sensitivity (Schizosaccharomyces pombe, Saccharomyces cerevisiae and Rhodotorula glutinis) after exposure to the Fenton reagent, FeII, H2O2, tert-butyl hydroperoxide (TBHP) and azo compounds (AAPH, ACHN). In whole cells, spontaneous TBRS formation rose in the sequence S. pombe < S. cerevisiae < R. glutinis (1:approximately 5:approximately 7). Oxidants increased the TBRS production 13-18 fold in the sequence FeII approximately TBHP > AAPH approximately ACHN approximately Fe-Fenton > H2O2. This increase need not be solely due to increased lipid peroxidation. In isolated plasma membrane lipids from all three species, the spontaneous TBRS production referred to 1 mg lipids was 9-13-fold higher than in whole cells. In S. pombe lipids, only TBHP increased the TBRS production. In lipids from S. cerevisiae and R. glutinis, all added oxidants increased the spontaneous TBRS production 2-3 times in the sequence TBHP > ACHN > AAPH > FeII > Fe-Fenton > H2O2. Oxidant-induced TBRS production in both whole cells and isolated membrane lipids was partially suppressed by the lipid peroxidation inhibitors 2,6-di-tert-butyl-4-methylphenol ("butylated hydroxytoluene"; BHT) and the newly synthesized PYA12 compound. Both agents were more effective in isolated lipids than in whole cells and against OH.-producing than against ROO.- or RO.-producing oxidants. Yeast membrane lipids, which are generally poor in polyunsaturated fatty acids, are thus subject to perceptible lipid peroxidation.

New phenolic antioxidants of PYA and PYE class increase the resistance S. cerevisiae strain SP4, its SOD- and catalase-deficient mutants to lipophilic oxidants.

Was demonstrate the protection ability against reactive oxygen species afforded to S. cerevisiae (wild-type strain SP4 and its mutants deficient in major antioxidant enzymes--catalase T and A, CuZnSOD) by PYA and PYE, new groups of phenolic antioxidants (quaternary ammonium salts of dihydrocinnamic acid amino esters with different alkyl chains; synthesized in this laboratory). The survival of strains exposed to the lipophilic oxidation inducers tert-butyl hydroperoxide (TBHP) and 1,1'-azobis(4-cyclohexane carbonitrile) (ACCN) with or without antioxidant pretreatment was determined by plating. S. cerevisiae mutant deficient in SOD was found to be hypersensitive to TBHP and ACCN while the sensitivity of the strain deficient in catalase T and A was about the same as in the wild-type strain. A 1-h preincubation of cells of both the wild-type and the mutant strains with the phenolic antioxidants prior to exposure to TBHP or ACCN substantially increased the cell survival. The magnitude of protection depended on the strain and the length of the alkyl chain of the antioxidant; the best average protection against TBHP was provided by PYE and PYA compounds with 12- and 16-membered alkyl chains whereas PYE-8 and PYA-12 derivatives afforded the best average protection against ACCN.

Viability and formation of conjugated dienes in plasma membrane lipids of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Rhodotorula glutinis and Candida albicans exposed to hydrophilic, amphiphilic and hydrophobic pro-oxidants.

Effects of four lipid peroxidation-inducing pro-oxidants--amphiphilic tert-butyl hydroperoxide (TBHP), hydrophobic 1,1'-azobis(4-cyclohexanecarbonitrile) (ACHN), hydrophilic FeII and 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH)--on cell growth and on generation of peroxidation products in isolated plasma membrane lipids were determined in four yeast species (S. cerevisiae, S. pombe, R. glutinis and C. albicans) differing in their plasma membrane lipid composition. TBHP and ACHN inhibited cell growth most strongly, FeII and AAPH exerted inhibitory action for about 2 h, with subsequent cell growth resumption. S. cerevisiae strain SP4 was doped during growth with unsaturated linoleic (18:2) and linolenic (18:3) acids to change its resistance to lipid peroxidation. Its plasma membranes then contained some 30% of these acids as compared with some 1.3% of 18:2 acid found in undoped S. cerevisiae, while the content of (16:1) and (18:1) acids was lower than in undoped S. cerevisiae. The presence of linoleic and linolenic acids in S. cerevisiae cells lowered cell survival and increased the sensitivity to pro-oxidants. Peroxidation-generated conjugated dienes (CD) were measured in pure TBHP- and ACHN-exposed fatty acids used as standards. The CD level depended on the extent of unsaturation and the pro-oxidant used. The TBHP-induced CD production in a mixture of oleic acid and its ester was somewhat lower than in free acid and ester alone. In lipids isolated from the yeast plasma membranes, the CD production was time-dependent and decreased after a 5-15-min pro-oxidant exposure. ACHN was less active than TBHP. The most oxidizable were lipids from S. cerevisiae plasma membranes doped with linoleic and linolenic acids and from C. albicans with indigenous linolenic acid.

Suppression of radical-induced lipid peroxidation in a model system by alkyl esters of cinnamate quaternary ammonium salts.

Three new groups of phenolic antioxidants, quaternary ammonium salts with a phenol ring and alkyl chains of different length (pyrrolidine ethyl esters of 3,5-di-t-butyl-4-hydroxydihydrocinnamic acid n-alkoxymethylchlorides (PYE-n) or n-alkylbromides (PYA-n) and 2-dimethylaminoethyl ester n-alkylbromides (PPA-n), were synthesized. Some of them were previously found to efficiently protect yeast cells against oxidants and to inhibit the production of thiobarbituric acid-reactive substances in whole yeast cells and in isolated membrane lipids. The new antioxidants (at 1-100 microM) abolished or diminished peroxidation of olive oil emulsions caused by the OH*-producing Fe2+ and RO* and ROO*-producing tert-butylhydroperoxide (TBHP) and the azo compounds 2,2'-azobis-(amidinopropane)dihydronitrile (AAPH) and 1,1'-azobis-(1-cyclohexanecarbonitrile) (ACHN): all present at 10 mM. The efficiency of individual both antioxidants was examined in relation to the type of lipid peroxidation inducer, the site of antioxidant incorporation into the emulsion lipid phase, the length of the alkyl chain, and the maximum concentration of effective antioxidant monomers given by its critical micelle concentration. PYA-n class compounds were highly efficient against all peroxidation inducers and their efficiency did not depend on the position of their molecules in the lipid phase and/or on the aliphatic chain length. In contrast, the efficiency of PYE-n and PPA-n class compounds depended both on the type of oxidant and on the length of their aliphatic chain. Their potency against Fe2+ and ACHN increased with increasing alkyl chain length whereas with AAPH it dropped with increasing alkyl chain length. A similar pattern was found with the action of PYE-n against TBHP whereas in the PPA-n group an extending alkyl chain reduced the anti-TBHP efficiency. These relationships may not be entirely straightforward and other factors (chemical nature of each compound, its possible interaction with fluorescent probes used for diagnostics, etc.) may play a considerable and not yet quite clear role. PPA-n class antioxidants have the lowest critical micelle concentration, which may limit their efficiency. Nevertheless, these phenolic antioxidants can be conveniently employed as highly efficient inhibitors of lipid peroxidation.

[Severity of angina pectoris and coronary angiographic imaging]. / Nasilenie dusznicy bolesnej a obraz koronariograficzny naczyn wiencowych.

The aim of the study was to evaluate commonly accepted assumption that more extensive coronary lesions correspond to more severe coronary symptoms. 300 consecutive patients with coronary artery disease (74 women and 226 men) admitted to Department of Coronary Disease in 1993/94 were studied. Coronary symptoms were assessed according to the Canadian Cardiovascular Society (CCS) classification of angina pectoris. Anatomic lesions revealed by angiography were classified as one, two or three vessel disease and also with use of Califfs jeopardy score (0-12 points) which is the simple and more precise method of estimating the amount of myocardium at risk. We found significant but rather weak correlation between severity of coronary symptoms (CCS) and angiographic findings (jeopardy score): (r = 0.16, p = 0.07). It was shown that there is the significant correlation between symptoms severity and anatomic lesions revealed by angiography. 17% of patients in spite of the extensive coronary atherosclerosis (10-12 points according to Califf) were almost asymptomatic (I class CCS). It is emphasized that one third of the patients had no critical stenosis however 51% of them presented severe coronary symptoms (III, IV class CCS).

History of sexual abuse and suicide attempts in alcohol-dependent patients.

History of child abuse is considered one of the important risk factors of suicide attempt in general population. At the same time it has been shown that suicide attempts appear significantly more frequently in alcoholics than in healthy individuals. The objective of this study was to investigate associations between history of childhood sexual abuse and suicide attempts in a sample of Polish alcohol dependent patients. A sample of 364 alcohol-dependent subjects was recruited in alcohol treatment centers in Warsaw, Poland. Information was obtained about demographics, family history of psychiatric problems, history of suicide attempts, sexual and physical abuse during childhood and adulthood and severity of alcohol problems. When analyzed by gender, 7.4% of male and 39.2% of female patients had a lifetime history of sexual abuse; 31.9% of the study group reported at least one suicide attempt during their lifetime. Patients who reported suicide attempts were significantly younger (p=0.0008), had greater severity of alcohol dependence (p=0.0002), lower social support (p=0.003), and worse economic status (p=0.002). Moreover, there was a significant association between history of suicide attempts and family history of psychiatric problems (p=0.00025), suicide attempts in the family (p=0.0073), childhood history of sexual abuse (p=0.009) as well as childhood history of physical abuse (p=0.002). When entered into linear regression analysis with other dependent variables history of childhood sexual abuse remained a significant predictor of suicide attempt (OR=2.52; p=0.035). Lifetime experience of sexual abuse is a significant and independent risk factor of suicide attempts in alcohol-dependent individuals.

Joint effects of dietary cadmium and polychlorinated biphenyls on metallothionein induction, lipid peroxidation and histopathology in the kidneys and liver of bank voles.

Free-living bank voles have been shown to be more sensitive to cadmium (Cd) toxicity than the rodents exposed to Cd under laboratory conditions. The present study was designed to find out whether polychlorinated biphenyls (PCBs), common environmental co-contaminants, increase susceptibility to Cd toxicity through inhibition of metallothionein (MT) synthesis-a low molecular weight protein that is considered to be a primary intracellular component of the protective mechanism. For 12 weeks, the male bank voles were provided with diets containing Cd (0.05 microg/g (control) and 10 microg/g dry wt) and PCBs (0, 10 and 50 microg/g dry wt) alone or in combination under long (16 h) and short (8 h) photoperiods. At the end of exposure period, histological examinations and analyses of MT, Cd, Fe and lipid peroxidation in the kidneys and liver were carried out. Dietary PCBs did not affect Cd inducibility of renal MT, but decreased it significantly in the liver; however, no signs of Cd toxicity (measured by histopathology) occurred in both organs. On the contrary, PCBs at the highest dose increased significantly lipid peroxidation in the kidneys and liver (4-fold) only in the bank voles raised under a long photoperiod; the PCB-induced hepatic lipid peroxidation was accompanied by extensive histopathological changes including hepatocyte enlargement, necrosis and steatosis. Co-treatment with dietary Cd significantly suppressed the increase in lipid peroxidation and apparently reduced hepatic damage. These data indicate that (1) dietary PCBs do not enhance Cd toxicity in the kidneys and liver of bank voles and (2) dietary Cd suppresses PCB-induced hepatotoxicity that appears to be photoperiod-dependent.