Melatonin inhibits neural apoptosis induced by homocysteine in hippocampus of rats via inhibition of cytochrome c translocation and caspase-3 activation and by regulating pro- and anti-apoptotic protein levels

In the present study, we examined the molecular mechanism by which homocysteine causes neuronal cell apoptosis. We further investigated the mechanisms of melatonin's ability to reduce homocysteine-induced apoptosis. Consistent with its antioxidant properties, melatonin reduced homocysteine-induced lipid peroxidation and stimulated glutathione peroxidase enzyme activity in hippocampus of rats with hyperhomocysteinemia. Furthermore, melatonin treatment diminished cytochrome c release from mitochondria and reduced caspase 3 and caspase 9 activation induced by hyperhomocysteinemia. Chronic hyperhomocysteinemia also led to poly(ADP-ribose) polymerase cleavage and subsequently DNA fragmentation. Treatment with melatonin markedly inhibited poly(ADP-ribose) polymerase cleavage and reduced DNA damage. Hyperhomocysteinemia caused an elevation of pro-apoptotic Bax levels while reducing anti-apoptotic protein, Bcl-2, levels. Daily administration of melatonin up-regulated Bcl-2 and down-regulated Bax levels. We propose that, in addition to its antioxidant properties, melatonin has the ability to protect neuronal cells against apoptosis mediated homocysteine neurotoxicity by modulating apoptosis-regulatory proteins in the hippocampus of rats.     

Oxidative Stress in Bacterial Meningitis

Fifty years after the advent of antibiotics for clinical use, the rates of morbidity and mortality associated with bacterial meningitis remain high. The unfavourable clinical outcome is often due to intracranial complications including cerebrovascular insults, raised intracranial pressure, hydrocephalus, and brain edema. Reactive oxygen species (ROS) are known effector molecules in the antimicrobial armature of polymorphonuclear and mononuclear phagocytes. However, over the last decade, there has been a substantial body of work implicating a central role of ROS in the development of intracranial complications and brain damage in bacterial meningitis. Recently, it also became evident that reactive nitrogen species (RNS), especially nitric oxide, are important mediators of meningitis-associated pathophysiological changes, at least during the early phase of the disease. There is now substantial evidence that much of the oxidative injury associated by simultaneous production of superoxide and nitric oxide is mediated by the strong oxidant peroxynitrite. ROS and peroxynitrite can be cytotoxic via a number of independent mechanisms. Their cytotoxic effects include initiation of lipid peroxidation and induction of DNA single strand breakage. Damaged DNA activates poly(ADP-ribose) polymerase (PARP). Recent experimental data propose a role of lipid peroxidation and PARP activation in the development of meningitis-associated intracranial complications and brain injury. Agents which interfere with the production of ROS and peroxynitrite, as well as with PARP activation and lipid peroxidation may represent novel, therapeutic strategies to limit meningitis-associated brain damage, and, thus, to improve the outcome of this serious disease.     

Amelioration of oxidative stress with ensuing inflammation contributes to chemoprevention of H. pylori-associated gastric carcinogenesis

The gastric inflammatory response provoked by Helicobacter pylori (H. pylori) consists of infiltrations by neutrophils, lymphocytes, and macrophages, resulting in varying degrees of epithelial cell damage. H. pylori-associated inflammation not only activates various oxidant-producing enzymes such as NADPH oxidase and inducible nitric oxide synthase, but also lowers the antioxidant ascorbic acid in the stomach. Reactive oxygen metabolites and nitrogen metabolites generated by these enzymes react with each other to generate new or more potent reactive species. The specific types of cellular damage resulting from reactive oxygen metabolites include lipid peroxidation, protein oxidation, and oxidative DNA damage. All of these oxidative products can result in biochemical changes leading to cancer. A positive association has been demonstrated between H. pylori infection and gastric adenocarcinoma with increased oxidative stress. Therefore, appropriate treatment to reduce oxidative stress would be expected to prevent subsequent gastric carcinogenesis through lessening of H. pylori-associated inflammation. This review will provide evidence that antiinflammatory regimens can decrease the development of tumors and the amelioration of gastric inflammation might lead to chemoprevention strategies by the attenuation of oxidative stress.     

Amelioration of sodium arsenite-induced clastogenicity by tea extracts in Chinese hamster v79 cells.

Since the early 1980s, an alarming problem of groundwater arsenic (As) contamination has devastated many districts of West Bengal in India. People drinking As-contaminated water have been suffering severe health problems such as hyperkeratosis, blackfoot disease, neuropathy, and cancer of various sites. DNA damage and genetic instability induced by the inorganic arsenicals present in water are thought to be prerequisites for the initiation of carcinogenesis. Many natural polyphenols, which are consumed through our daily diet, possess excellent cancer chemopreventive properties. Tea, a popular beverage worldwide and rich in polyphenols, has exhibited many health benefits. The present study was conducted to examine the anticlastogenic action of tea extracts (both green and black) against the As-induced chromosomal aberrations. We also evaluated the role of tea in inducing antioxidant enzymes such as superoxide dismutase and catalase to provide protection against the oxidative stress induced by As. Our results demonstrated that tea extracts, particularly Darjeeling tea extract, are effective in counteracting the clastogenicity (chromatid breaks, in particular) of the most potent form of As, sodium arsenite. The antioxidant function of tea in reducing clastogenicity may be partly due to the induction of phase II detoxification enymes, such as superoxide dismutase and catalase. Our results suggest that the use of tea may be an effective approach in combating the health crisis generated by As.     

Arsenic-induced micronuclei formation in mammalian cells and its counteraction by tea.

The Gangetic plain of West Bengal, India, has been engulfed by a disastrous environmental calamity of arsenic contamination of the ground water. Chronic arsenic toxicity caused by drinking arsenic-contaminated water has been one of the worst health hazards gradually affecting nine districts of West Bengal since the early 1980s. Over and above hyperpigmentation and keratosis,weakness, burning sensation of the eyes, swelling of the legs, liver fibrosis, chronic lung disease, gangrene of the toes, neuropathy, and skin cancer are other manifestations. Induction of cancer is frequently associated with DNA damage, changes in ploidy of cells, and non-random chromosome aberrations. Counteraction of these genotoxic and cytogenetic abnormalities with natural dietary polyphenols could be a useful strategy to combat arsenic-induced DNA damage and thereby cancer. A review of the literature showed that it is the antioxidant property of tea polyphenols that affords protection against various types of cancer. The present study was conducted to investigate whether the extracts of green tea and black tea (Darjeeling and Assam) as well as their polyphenols could ameliorate this arsenic-induced genotoxicity. The normal mammalian cell culture derived from male Chinese hamster lung fibroblast cells (V79) was used as the test system to assess the genotoxicity by micronucleus assay. The results showed that both green tea and black tea extracts have equal potential in modulating the arsenic-induced genotoxicity. This effect was perhaps induced by the constituent polyphenols present in green and black tea. In addition, the repair activity of the damaged cells was enhanced when treated with these tea extracts and their polyphenols. Thus, tea and its polyphenols may have a promising role in counteracting the devastating effects of arsenic.     

Antioxidant potential of black tea against 7,12-dimethylbenz(a)anthracene- induced oxidative stress in Swiss albino mice.

Oxygen free radicals and related reactive species have been implicated in the etiology of many diseases, such as atherosclerosis, neurodegenerative disorders, and cancer. Antioxidant enzymes exist in cells to protect against the effects of these free radicals and other oxygen-derived species, which are produced during the oxidative stress. Tea (Camellia sinensis) is the most commonly consumed beverage worldwide. Both green and black tea are known to possess many pharmacological properties, including antioxidant, antipyretic, antibacterial, and antineoplastic effects. In the present study, the preventive effects of black tea extract (BTE) was evaluated in Swiss albino mice against 7,12-dimethyl benz(a)anthracene (DMBA)-induced oxidative stress. The animals were given 0.5%, 1%, and 1.5% BTE as the sole source of drinking solution for 1 week prior to the administration of DMBA, which was given orally as a single dose of 50 mg/kg body weight. At the end of the study period, the liver, kidney, and prostate tissues were dissected out for the determination of antioxidant enzyme levels (catalase, superoxide dismutase, glutathione reductase, glutathione-S-transferase), and lipid peroxidation. A dose-dependent protective effect of BTE against DMBA-induced depletion in enzymes activity was observed in all three tissues examined. Similarly, a significant dose-dependent inhibition of the lipid peroxidation caused by DMBA was observed in the BTE-administered animals in all three tissues examined. Our results revealed that BTE provides protection against oxidative damage induced by xenobiotics.     

Protective effects of Picorrhiza kurroa extract against 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats.

Picrorrhiza kurroa has been shown to impart significant hepatoprotective activities, partly by modulation of free radical--induced lipid peroxidation. Lipid peroxidation and reactive oxygen species are associated with hepatic injury. The effect of P. kurroa treatment on the antiproliferative response and, hepatic antioxidant enzymes of rats administered with 2-acetylaminofluorene (2-AAF) was studied in Wistar rats. 2-AAF (50 mg/kg body weight, i.p.) enhances hepatic lipid peroxidation, with reduction in hepatic glutathione content, glutathione peroxidase, glutathione reductase, catalase, and glutathione-s-transferase. There was an increase in the levels of transaminase enzymes and LDH. 2-AAF treatment also enhanced ornithine decarboxylase (ODC) activity and [3H] thymidine incorporation into hepatic DNA. Pretreatment of rats orally with P. kurroa extract (250 and 500 mg/kg body weight) resulted in significant decrease in lipid peroxidation, transaminase enzymes, LDH, hepatic ODC activity, and DNA synthesis (p < 0.001). Hepatic glutathione content (p < 0.001), glutathione metabolizing enzymes (p < 0.001), and antioxidant enzymes were also recovered to significant level (p < 0.001).     

Role of DNA polymerase beta in the genotoxicity of arsenic

Arsenic, an important hazard in the environment, is associated with human cancer and other degenerative diseases. However, the mechanisms underlying arsenic hazardous effects remain unclear. It has been reported arsenic exposure can result in increased cellular reactive oxygen species and oxidative DNA damage. This suggests DNA base excision repair (BER), the major pathway for repairing oxidative DNA damage, may be involved in combating arsenic hazardous effects. As a critical repair enzyme in BER, DNA polymerase beta (Pol β) might play an essential role in reducing arsenic toxicity. To test this hypothesis, we evaluated arsenic-induced cytotoxic and genotoxic effects under Pol β deficiency. Our results demonstrated that the viability of Pol β-deficient mouse embryonic fibroblasts was much lower than that of Pol β wild-type cells after treatment with arsenite (As(3+) ). An increased level of DNA damage and significantly delayed arsenite-induced DNA damage repair in Pol β-deficient cells indicated reduced repair of DNA lesions under Pol β deficiency. This was consistent with the increase in the frequency of micronuclei (MN), an indicator of chromosomal breakage, which was also observed in Pol β-deficient cells treated with arsenite. In contrast, cells harboring overexpressed Pol β resulted in a lower level of DNA damage and MN than Pol β wild-type cells, indicating overexpression of the enzyme can combat arsenic-induced genotoxic effects. In conclusion, our results indicate an important role for Pol β in repairing arsenite-induced DNA damage and maintaining chromosomal integrity and further suggest deficiency of BER may be involved in arsenic genotoxicity and carcinogenicity.     

Inhibition of lipid peroxidation and protein oxidation by endogenous and exogenous antioxidants in rat brain microsomes in vitro

Reactive oxygen and reactive nitrogen species oxidize and nitrate DNA, lipid and proteins thus leading to neuronal death. Both endogenous and dietary antioxidants were shown to afford neuroprotection either by scavenging free radicals or inducing antioxidant enzymes. That said, the differential contribution of endogenous versus nutritional antioxidants to prevent neurodegeneration is still debated. In this study the free radical scavenging activity of two endogenous antioxidants, such as bilirubin and its precursor biliverdin, was compared with that of the dietary antioxidant alpha-tocopherol in rat brain microsomes exposed to peroxyl radical or peroxynitrite in vitro. Bilirubin and biliverdin (1–200 μM) inhibited both peroxyl radical- and peroxynitrite-dependent lipid peroxidation with a greater potency and efficacy than alpha-tocopherol. However, both BV and BR displayed greater potency and efficacy in preventing peroxynitrite- than peroxyl radical-induced lipid peroxidation. The greater antioxidant effect of both bilirubin and biliverdin than alpha-tocopherol was also confirmed against peroxyl radical- and peroxynitrite-induced protein oxidation. In conclusion, both bilirubin and biliverdin exhibited a greater antioxidant activity than alpha-tocopherol in preventing oxidative stress damage in rat brain.     

Analysis of the impact of intracellular reactive oxygen species generation on the structural and functional integrity of human spermatozoa: lipid peroxidation, DNA fragmentation and effectiveness of antioxidants

Exposure of human spermatozoa to nicotinamide adenine dinucleotide phosphate (NADPH) resulted in the dose dependent generation of reactive oxygen species (ROS) which, at a critical level of intensity, induced lipid peroxidation, DNA damage and a dramatic decline of sperm motility. This system was then used as a model for screening the ability of different antioxidants to combat oxidative stress created through the excessive intracellular generation of toxic oxygen products of metabolism. A variety of antioxidants that has previously been shown to be protective against extracellularly derived oxidants (e.g. superoxide dismutase, catalase, vitamin E, hypotaurine) were ineffective in this system. Albumin, however, could provide complete protection against NADPH induced oxidative stress via mechanisms that did not involve the suppression of the lipid peroxidation cascade but rather the inactivation of lipid peroxides generated during this process. Albumin did not protect against DNA damage induced by NADPH but was extremely effective at preventing DNA fragmentation arising from the suppression of glutathione peroxidase activity with mercaptosuccinate. These studies emphasize that the design of clinically effective antioxidant treatments will depend, critically, upon the source of the oxidative stress. For cases involving excessive intracellular ROS generation, albumin appears to be an important means of neutralizing lipid peroxide-mediated damage to the sperm plasma membrane and DNA.      

Mammalian longevity under the protection of PARP-1's multi-facets

Given the presence of continuous endogenous and exogenous sources of stress, mammalian species have evolved complex systems of protection, detoxification and repair, in order to maintain homeostasis during development and until reproductive maturity for the sake of the species. However, since no system is perfect, complete prevention of damage is unlikely to occur. Accumulation of macromolecular damage, including damage to DNA and genomic instability, is considered a driving force for the ageing process and age-related diseases. One of the immediate eukaryotic cellular responses to DNA breakage is the covalent post-translational modification of nuclear proteins with poly(ADP-ribose) from NAD+ as precursor, mostly catalysed by poly(ADP-ribose) polymerase-1 (PARP-1). Poly(ADP-ribosyl)ation is involved in DNA base-excision repair (BER), DNA-damage signalling and regulation of genomic stability. In recent years, many groups have become involved in PARP field, shedding light on new partners for PARP-1, new members of the PARP family and new physiological and pathophysiological properties for the founding member of the poly(ADP-ribose) polymerase super family. The present review focuses on PARP-1 and its role in the maintenance of genome stability and in mammalian longevity.     

Antioxidative protection of dietary bilberry,chokeberry and <Emphasis Type="Italic">Lactobacillus plantarum</Emphasis> HEAL19 in mice subjected to intestinal oxidative stress by ischemia-reperfusion

Background  

Ischemia-reperfusion (I/R) in the intestines is an inflammatory condition which activates leukocytes and reactive oxygen species (ROS) and leads to lipid peroxidation and DNA damage. Bilberry and chokeberry fruits are rich sources of polyphenols which may act as antioxidants and prevent lipid peroxidation. Lactic acid bacteria (LAB) may improve microbial status in the intestines and increase the metabolic activity towards polyphenolic degradation. The aim of the study was to clarify antioxidative effects of bilberry and chokeberry fruits alone and with addition of a LAB-strain, Lactobacillus plantarum HEAL19, in an I/R-model in mice.     

Reactive oxygen species and antioxidant mechanisms in human tissues and their relation to malignancies

Reactive oxygen species (ROS) are formed in mammalian cells as a consequence of aerobic respiration. Despite multiple conserved redox modulating systems, a given proportion of ROS continuously escape from the mitochondrial respiratory chain, being sufficiently potent to damage cells in various ways, including numerous carcinogenic DNA mutations. Oxidative stress resulting from an imbalanced ratio between ROS production and detoxification may also disturb physiological signal transduction, lead to chain reactions in lipid layers, and damage DNA repair enzymes. The significance of ROS and antioxidant systems in carcinogenesis is still complicated and in many ways contradictory. Enhanced antioxidant mechanisms in tumor cells in vivo have been implicated in chemoresistance and lead to poor prognosis, whereas most in vitro studies have reported tumor-suppressing properties of antioxidant enzymes. The present review aims to clarify the significance of oxidative stress and the role of cell redox state modulating systems in human malignancies in light of the current literature.     

Inducible protective processes in animal systems. X. Influence of nicotinamide in methyl methanesulfonate-adapted mouse bone marrow cells.

The adaptive response is an error-free DNA repair mechanism induced by low levels of physical or chemical agents. Cells pre-exposed to such agents are resistant to genetic damage induced by subsequent treatment at a high dose. There are many reports on such adaptive responses. Recently we have shown the existence of adaptive responses in vivo in the grasshopper Poecilocerus pictus and the mouse and in vitro in human lymphocytes. Different enzymes are implicated in this DNA repair pathway. In an attempt to understand the molecular mechanism of the methyl methanesulfonate (MMS)-induced adaptive response, the present investigations have been undertaken employing nicotinamide, an inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP). Pre-, inter- and post-treatments with nicotinamide of MMS-treated mouse bone marrow cells were carried out. The results revealed that there is a significant reduction in the frequency of chromosomal aberrations compared with combined treatment, suggesting an enhancement of the adaptive response by nicotinamide. Further, the results of NAD+ assay in the inter-treatment experiment showed that there is no depletion of NAD+. Thus, it can be stated that PARP is not involved in the MMS-induced adaptive response in mouse bone marrow cells.     

Human umbilical cord blood-derived mesenchymal stem cells undergo cellular senescence in response to oxidative stress

Since human mesenchymal stem cells (MSCs) are therapeutically attractive for tissue regeneration and repair, we examined the physiological responses of human umbilical cord blood-derived MSCs (hUCB-MSCs) to genotoxic stress. We found that that sublethal doses of reactive oxygen species (ROS) and ionizing radiation cause DNA damage and reduce DNA synthesis and cell proliferation in hUCB-MSCs, resulting in cellular senescence. In contrast, these physiological changes were limited in human fibroblast and cancer cells. Our data show that reduced activities of antioxidant enzymes, which may occur due to low gene expression levels, cause hUCB-MSCs to undergo cellular senescence in response to oxidative stress and ionizing radiation. Resistance of hUCB-MSCs to oxidative stresses was restored by increasing the intracellular antioxidant activity in hUCB-MSCs via exogenous addition of antioxidants. Therefore, the proliferation and fate of hUCB-MSCs can be controlled by exposure to oxidative stresses.     

Antagonistic role of tea against sodium arsenite-induced oxidative DNA damage and inhibition of DNA repair in Swiss albino mice

Arsenic (As) contamination in groundwater is of increasing health concern in West Bengal, India. Arsenic has been associated with various human cancers, but the precise mechanism of its co-carcinogenic action is not clearly elucidated. Oxidative stress and defective repair mechanisms may promote accumulation of mutations and may be a stepping stone for carcinogenesis. Prevention of arsenic-induced oxidative stress and repair inhibition may reduce the chances of initiation of cancer. Tea polyphenols are reported to have excellent chemopreventive properties against cancer. This study aimed to elucidate the role of tea against arsenic-induced formation of 8-hydroxy-2'-deoxyguanosine (8OHdG) and arsenic-suppressed DNA repair in Swiss albino mice. Both green and black tea gave fruitful results in the reduction of 8OHdG and 8-oxoguanine DNA glycosylase (OGG1) in Swiss albino mice administered sodium arsenite (As III). DNA repair enzymes--such as PARP1, DNA β-polymerase, XRCC1, DNA ligase III, DNA protein kinase (catalytic subunit), XRCC 4, DNA ligase IV, and DNA topoisomerase IIβ--were induced by the phytochemicals at both the protein and genetic levels. Thus, tea polyphenols may prove effective in treating arsenic-induced carcinogenesis.     

Free radical scavenging, DNA protection, and inhibition of lipid peroxidation mediated by uric acid

Uric acid (UA) has been proposed to be the dominant antioxidant in birds. The objective of this study was to investigate the quenching effect of varying concentrations of UA, including those found in avian plasma, on specific reactive oxygen species (ROS) and to determine the ability of UA to protect DNA and cellular membranes from ROS-mediated damage. Hydroxyl (OH) and superoxide (O2-) radicals were detected by electron spin resonance (ESR) and their presence was reduced following addition of UA (p <0.05) in a concentration-dependent manner. UA inhibited hydroxyl-mediated DNA damage, indicated by the presence of more precise, dense bands of lambda Hind III DNA after agarose gel electrophoresis and ethidium bromide staining (p <0.05). Lipid peroxidation of silica-exposed RAW 264.7 cell membranes was diminished (p <0.02) after addition of UA to the cell incubation mixture. These studies demonstrate that UA scavenges hydroxyl and superoxide radicals and protects against DNA damage and lipid peroxidation. These results indicate specific antioxidant protection that UA may afford birds against ROS-mediated damage.     

Black tea-induced amelioration of hepatic oxidative stress through antioxidative activity in EAC-bearing mice.

It is recognized that during cancer, the disease itself as well as many of the anticancer drugs in use produce undesirable side effects such as hepatotoxicity. We have already demonstrated the antitumor and immunorestoring effects of black tea. Here we report Ehrlich's ascites carcinoma (EAC)induced hepatotoxicity and its protection by antitumor dose of black tea in mice. Hepatotoxicity was adjudged by liver histopathology and by measurement of plasma level of alkaline phosphatase (ALP). An attempt to delineate the underlying mechanisms revealed tumor-induced generation of reactive oxygen species (ROS) on one hand and depression in antioxidants that neutralize ROS, i.e., superoxide dismutase (SOD), catalase, reduced glutathione (GSH), and glutathione-S-transferase (GST), on the other. As a result, lipid peroxidation, which leads to damage of host cell components, was increased. Treatment with antitumor dose of black tea could replenish the host's antioxidant system and regress cancer-induced ROS significantly, thereby protecting the host's liver from lipid peroxidation and subsequent degeneration. Thus, unlike many other anticancer agents, black tea not only has antitumor and immunorestoring properties, but it also protects host liver from tumor-induced toxicity. These results thus raise the possibility of inclusion of black tea in a successful therapeutic regimen against cancer.     

Correlation of mitochondrial superoxide dismutase and DNA polymerase beta in mammalian dermal fibroblasts with species maximal lifespan

Eukaryotic cells have evolved elaborate mechanisms to preserve the fidelity of their genomic material in the face of chronic attack by reactive byproducts of aerobic metabolism. These mechanisms include antioxidant and DNA repair enzymes. Skin fibroblasts of long-lived mammalian species are more resistant to oxidative stress than those of shorter-lived species [Kapahi, P., Boulton, M.E., Kirkwood, T.B., 1999. Positive correlation between mammalian life span and cellular resistance to stress. Free Radic. Biol. Med. 26, 495-500], and we speculated that this is due to greater antioxidant and/or DNA repair capacities in longer-lived species. We tested this hypothesis using dermal fibroblasts from mammalian species with maximum lifespans between 5 and 122 years. The fibroblasts were cultured at either 18 or 3% O(2). Of the antioxidant enzymes only manganese superoxide dismutase was found to positively correlate with maximum lifespan (p<0.01). Oxidative damage to DNA is primary repaired by the base excision repair (BER) pathway. BER enzyme activities showed either no correlation (apurinic/apyrimidinic endonuclease), or correlated negatively (p<0.01) with donor species MLS (polymerase beta). Standard culture conditions (18% O(2)) induced both antioxidant and BER enzymes activities, suggesting that the 'normal' cell culture conditions widely employed are inappropriately hyperoxic, which likely confounds the interpretation of studies of cellular oxidative stress responses in culture.     

Use of black tea in modulating clastogenic effects of arsenic in mice in vivo.

The concentration of arsenic in drinking water has far exceeded the permissible limit of 0.001 mg/L and has reached epidemic proportions, with a maximum of 3.7 mg/L in several districts of West Bengal and in the adjoining Bangladesh. Because inorganic arsenic is a documented human carcinogen, arsenic in drinking water may cause 200,000-270,000 deaths per year from cancer in India alone. Tea has a protective effect against the clastogenicity of arsenic. We investigated whether tea extracts could protect against the damage caused by arsenic in vivo. Our experiments were carried out with black tea in mice with the end points of incidence of chromosomal aberrations and damaged cells. Analysis of variance of chromosomal aberrations showed a significant difference in the toxic effects of arsenic, which were reduced by tea infusion. The frequency of chromosomal aberrations was close to the corresponding effects of tea alone. Continued dietary administration of black tea infusion protects against the chromosome-damaging effects of sodium arsenite at a statistically significant level. The degree of protection increases with duration of tea consumption, which may be attributed to the antioxidant and scavenging properties of tea infusion.