DNA Damage Activity Research Articles

Application of semipermeable membrane device (SPMD) to assess air genotoxicity in an occupational environment

Semipermeable membrane device (SPMD) is a passive sampler that sequesters lipophilic contaminants, mimicking the bioconcentration in the fatty tissue of organisms. This study was designed to assess the use of SPMD and biological tests (Comet assay and Ames test) for air monitoring. For this purpose an occupational environment with expected polycyclic aromatic hydrocarbons (PAHs) contamination (coke plant) was selected for a case study. The SPMDs were deployed in five occupational contaminated sites and in a control site. The SPMD dialysates were chemically analysed and examined for in vitro DNA-damaging activity in human cells (Jurkat) by Comet assay and for mutagenicity with the Ames test (TA98 strain, w/o S9). Total suspended particulates were also collected and analysed (GC–MS). No biological effect of SPMD extract was revealed in the control site. On the other hand, air samples collected with SPMDs within the coke plant showed variable degrees of genotoxic and mutagenic activity. The highest effects were associated with the highest PAH level recovered in the SPMDs extracts and in particulate samples. Results obtained support the sensitivity of biological tests associated to SPMD sampling for evaluating the health risk of potentially contaminated work environments highlighting the usefulness of SPMDs for environmental air quality monitoring.

Biological activities of steroidal alkaloids isolated from Solanum leucocarpum

The alkaloids demissidine, dihydrosolacongestidine, solasodine and tomatidine were isolated and identified by spectroscopic methods and by comparison with literature data, from the aerial part of Solanum leucocarpum Dunal (Solanaceae) collected at the Regional Natural Park Ucumarí (Colombia). In order to examine topoisomerase I and II activities, the four isolated alkaloids were tested through a mechanism-based bioassay utilizing genetically engineered mutants of yeast Saccharomyces cerevisiae strains RS322N, R52Y and RS321. Dihydrosolacongestidine showed selective activity towards RS321 (249.8 μg/mL) strain rather than RS322N (1542.7 μg/mL), most probably indicating activity through inhibition of DNA topoisomerase II. In the same manner, tomatidine displayed activity through DNA topoisomerase II inhibition. Furthermore, solasodine showed DNA-damaging activity. In addition, the same isolated alkaloids were tested for antibacterial activity by using the agar well diffusion method. Solasodine and dihydrosolacongestidine showed MIC values of 62.5 and 125 μg/mL against Staphylococcus aureus, respectively. The isolation of these alkaloids and their biological activities are reported here for the first time for S. leucocarpum.

Synthesis and antitumor activity of optically active thiourea and their 2-aminobenzothiazole derivatives: A novel class of anticancer agents

A novel series of optically active 2-aminobenzothiazole derivatives were synthesized by reaction of optically active amine ( I) with thiophosgene to obtain optically active isothiocyanates ( IIa– h) which on condensation with 4-fluoro-3-chloro aniline ( III) yielded various optically active thioureas ( IVa– h). Further oxidative cyclisation in the presence of bromine and chloroform yielded title compounds ( Va– h). The structures of these compounds were established by IR, 1H NMR, 13C NMR, Mass and HRMS. The compounds ( IVa– h and Va– h) were evaluated for in vitro cytotoxicity against mouse Ehrlich Ascites Carcinoma (EAC) and two human cancer cell lines (MCF-7 and HeLa). In preliminary MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity studies the optically active thiourea derivatives ( IVe, IVf and IVh) were found most effective. In EAC cells the IC 50 values for IVe, IVf, IVh and Vg were found in the range of 10–24 μM, whereas in MCF-7 and HeLa cells the IC 50 values were observed in the range of 15–30 μM and 33–48 μM, respectively. In alkaline comet assay the compounds ( IVe and IVf) showed dose-dependent DNA damaging activity.

Screening for antifungal, DNA-damaging and anticholinesterasic activities of Brazilian plants from the Atlantic Rainforest: Ilha do Cardoso State Park

Crude extracts from 17 plant species collected from an Atlantic Forest region in the State of São Paulo (Brazil) have been screened for antifungal, DNA-damaging and acetylcholinesterase inhibiting activities. Of the 34 extracts obtained from leaves and stems of plants assayed for antifungal activity with Cladosporium sphaerospermum and C. cladosporioides 26.5% were active. However, only the extract of leaves of Cabralea canjerana showed a strong inhibition of both fungi. The DNA-damaging assay with mutant strains of Saccharomyces cerevisiae resulted in 11.7 % of the extracts being active whereas 100% of them showed selectivity for the DNA-repair mechanism of topoisomerase II. Of the 17 species analysed, 12 showed anticholinesterasic activity in TLC assay. However, only extracts from Tetrastylidium grandifolium (stems) and Sloanea guianensis (leaves and stems) inhibited acetylcholinesterase activity more than 50% in quantitative assay.

DNA damage and metabolic activity in the preimplantation embryo

Embryos with greater viability have a lower or 'quieter' amino acid metabolism than those which arrest. We have hypothesized this is due to non-viable embryos possessing greater cellular/molecular damage and consuming more nutrients, such as amino acids for repair processes. We have tested this proposition by measuring physical damage to DNA in bovine, porcine and human embryos at the blastocyst stage and relating the data to amino acid profiles during embryo development. Amino acid profiles of in vitro-derived porcine and bovine blastocysts were measured by high-performance liquid chromatography and the data related retrospectively to DNA damage in each individual blastomere using a modified alkaline comet assay. Amino acid profiles of spare human embryos on Day 2-3 were related to DNA damage at the blastocyst stage. A positive correlation between amino acid turnover and DNA damage was apparent when each embryo was examined individually; a relationship exhibited by all three species. There was no relationship between DNA damage and embryo grade. Amino acid profiling of single embryos can provide a non-invasive marker of DNA damage at the blastocyst stage. The data are consistent with the quiet embryo hypothesis with viable embryos (lowest DNA damage) having the lowest amino acid turnover. Moreover, these data support the notion that metabolic profiling, in terms of amino acids, might be used to select single embryos for transfer in clinical IVF.

DNA damage and effects on antioxidative enzymes in earthworm ( Eisenia foetida) induced by atrazine

To evaluate atrazine (2-chloro-4-ethylamino-6-isopropylamino-1, 3, 5-triazine) ecotoxicology in soil, the effect of atrazine on the activity of antioxidative enzymes (superoxide dismutase, SOD; catalase, CAT; and guaiacol peroxidase, POD) and DNA damage induced by atrazine were investigated in earthworms. Atrazine was added to artificial soil at rates of 0, 2.5, 5 and 10 mg per kg of soil. Earthworm tissues exposed to each treatment were collected on the 7th, 14th, 21st, and 28th day of the treatment. Compared to the controls, the CAT activity was stimulated at 2.5 mg kg −1 treatment except on the 14th day, and inhibited at 5, 10 mg kg −1 atrazine except 5 mg kg −1 on the 28th day and 10 mg kg −1 on the 21st day; the overall SOD activity was inhibited, while the POD activities were stimulated by all atrazine concentrations in 28 days. The olive tail moments of single-cell gel electrophoresis of coelomocytes, as an indication of DNA damage, were increased after treatment with different doses of atrazine on the 7th, 14th, 21st, and 28th day, and significant differences were found compared to the controls. In conclusion, atrazine induces oxidative stress and DNA damage on earthworms, and the adverse effects may be the important mechanisms of its toxicity to earthworms.

Abrin induced oxidative stress mediated DNA damage in human leukemic cells and its reversal by N-acetylcysteine

Abrin is a plant glycoprotein toxin, classified as ribosome inactivating protein (RIP) due to its property of damaging ribosomes in an irreversible manner. Many RIPs have direct DNA damaging activity. The objective of the present study was to evaluate the oxidative stress and DNA damaging potential of abrin in U937 human myeloleukemic cells. Cells were treated with abrin at IC50 of 8 ng/ml for 24h. Abrin induced a time dependent increase in reactive oxygen species and levels of antioxidant enzymes. There was significant depletion of reduced glutathione levels. DNA damage was assessed by comet assay in terms of percent head DNA, tail DNA, tail length and Olive tail moment. DNA damage was more pronounced at 4 and 8h at IC50 concentration. Abrin at 4, 8, 16 and 32 ng/ml concentration induced significant DNA damage at 4h. There was time dependent increase in levels of 8-OHdG in abrin treated cells indicating the oxidative stress mediated DNA damage. N-Acetylcysteine pretreatment at 10nM for 1h, considerably reversed the abrin induced DNA damage at 16 and 32 ng/ml. Our results clearly show oxidative DNA damage potential of abrin at low concentration.

Biochemical markers of male infertility: the key role of DNA damage

One product resulting from free radical damage is DNA hydroxylation, also known as DNA oxidation and DNA fragmentation. DNA oxidative damage is indicative of a number of conditions involving the generation of oxygen free radicals. This damage could be the primary source of DNA fragmentation. We will overview some of the conditions in which this phenomenon is present and we will focus the major part of this review describing the methods to study DNA damage and the implications of this phenomenon in male infertility, most of them reflected in the IVF outcome. Finally, we will describe which could be factors related with DNA damage, including chemicals, radiation, diseases and normal metabolic activity.

Loss of miRNA biogenesis induces p19Arf-p53 signaling and senescence in primary cells

Dicer, an enzyme involved in microRNA (miRNA) maturation, is required for proper cell differentiation and embryogenesis in mammals. Recent evidence indicates that Dicer and miRNA may also regulate tumorigenesis. To better characterize the role of miRNA in primary cell growth, we generated Dicer-conditional mice. Ablation of Dicer and loss of mature miRNAs in embryonic fibroblasts up-regulated p19Arf and p53 levels, inhibited cell proliferation, and induced a premature senescence phenotype that was also observed in vivo after Dicer ablation in the developing limb and in adult skin. Furthermore, deletion of the Ink4a/Arf or p53 locus could rescue fibroblasts from premature senescence induced by Dicer ablation. Although levels of Ras and Myc oncoproteins appeared unaltered, loss of Dicer resulted in increased DNA damage and p53 activity in these cells. These results reveal that loss of miRNA biogenesis activates a DNA damage checkpoint, up-regulates p19Arf-p53 signaling, and induces senescence in primary cells.

Induction of tumor cell apoptosis by a novel class of N-thiolated β-lactam antibiotics with structural modifications at N1 and C3 of the lactam ring

The investigation of novel anti-tumor agents that preferentially select for malignant cells with a tolerable toxicity level has been the focus of anti-cancer drug discovery. Our laboratories have previously reported that certain N-alkylthiolated beta-lactams had DNA-damaging and apoptosis-inducing activity in various tumor lines but not in nontransformed cells. In the current study, we further delineated the effects of substitutions at C3 or N1 of the lactam ring for cell death-inducing capability with close attention paid to a discernible structure-activity relationship (SAR). We found that two beta-lactam analogs (JG-5 and JG-19), both containing a branched-chain moiety at C3 of the lactam ring, exhibit potent apoptosis-inducing activity. Additionally, JG-5 exhibited superior in vitro biological activity over JG-19 owing to structural modifications made to substituents at the N1 and C3 positions of the lactam ring. Furthermore, the branched beta-lactams were able to inhibit growth of mice bearing breast cancer xenografts, associated with induction of DNA damage and apoptosis in tumor tissues. Our results strongly warrant further investigation into these novel beta-lactams as potential anti-cancer therapeutics.

Oxidative stress, DNA damage, and antioxidant enzyme activity induced by hexavalent chromium in Sprague‐Dawley rats

Chromium is a widespread industrial compound. The soluble hexavalent chromium Cr (VI) is an environmental contaminant widely recognized as carcinogen, mutagen, and teratogen toward humans and animals. The fate of chromium in the environment is dependent on its oxidation state. The reduction of Cr (VI) to Cr (III) results in the formation of reactive intermediates leading to oxidative tissue damage and cellular injury. In the present investigation, Potassium dichromate was given intraperitoneally to Sprague-Dawley rats for 5 days with the doses of 2.5, 5.0, 7.5, and 10 mg/kg body weight per day. Oxidative stress including the level of reactive oxygen species (ROS), the extent of lipid peroxidation and the activity of antioxidant enzymes in both liver and kidney was determined. DNA damage in peripheral blood lymphocytes was determined by single-cell gel electrophoresis (comet assay). The results indicated that administration of Cr (VI) had caused a significant increase of ROS level in both liver and kidney after 5 days of exposure, accompanied with a dose-dependent increase in superoxide dismutase and catalase activities. The malondialdehyde content in liver and kidney was elevated as compared with the control animals. Dose- and time-dependent effects were observed on DNA damage after 24, 48, 72, and 96 h posttreatment. The results obtained from the present study showed that Cr (VI) could induce dose- and time-dependent effects on DNA damage, both liver and kidney show defense against chromium-induced oxidative stress by enhancing their antioxidant enzyme activity. However, liver was found to exhibit more antioxidant defense than the kidney.

DNA repair phenotype and dietary antioxidant supplementation

Phytochemicals may protect cellular DNA by direct antioxidant effect or modulation of the DNA repair activity. We investigated the repair activity towards oxidised DNA in human mononuclear blood cells (MNBC) in two placebo-controlled antioxidant intervention studies as follows: (1) well-nourished subjects who ingested 600 g fruits and vegetables, or tablets containing the equivalent amount of vitamins and minerals, for 24 d; (2) poorly nourished male smokers who ingested 500 mg vitamin C/d as slow- or plain-release formulations together with 182 mg vitamin E/d for 4 weeks. The mean baseline levels of DNA repair incisions were 65.2 (95 % CI 60.4, 70.0) and 86.1 (95 % CI 76.2, 99.9) among the male smokers and well-nourished subjects, respectively. The male smokers also had high baseline levels of oxidised guanines in MNBC. After supplementation, only the male smokers supplemented with slow-release vitamin C tablets had increased DNA repair activity (27 (95 % CI 12, 41) % higher incision activity). These subjects also benefited from the supplementation by reduced levels of oxidised guanines in MNBC. In conclusion, nutritional status, DNA repair activity and DNA damage are linked, and beneficial effects of antioxidants might only be observed among poorly nourished subjects with high levels of oxidised DNA damage and low repair activity.

Protective role of curcumin against nicotine-induced genotoxicity on rat liver under restricted dietary protein

Nicotine, the well known addictive chemical of tobacco and active medication for several diseases, has proven to be a potential genotoxic compound. Although it is absorbed through lungs with smoking and mainly metabolized in liver, its effect on liver injuries is not clear. This study was designed to evaluate the genotoxicity of nicotine and corresponding the protective role of curcumin against nicotine on liver of female populations particularly who used tobacco but deprived of healthy diet. The effects were investigated by measurement of total DNA concentration of liver tissues and Comet assay of liver tissue DNA damage of female rats maintained under normal and restricted protein diets. Total DNA contents in the liver tissues were observed to decrease more significantly ( P < 0.001) by nicotine in both dietary conditions. Significant ( P < 0.01) increase of total DNA content in normal dietary condition and more significant ( P < 0.001) increase of total DNA content in protein restricted condition of the liver tissues were observed due to curcumin supplementations. Highly significant ( P < 0.001) DNA damages (37% in normal diet and 56% in protein restricted diet) of the liver tissues were observed due to nicotine treatment. Curcumin reduced the nicotine-induced DNA damage percentage of the liver tissues more significantly ( P < 0.001) in protein restricted condition. Curcumin proved its potential to function against genotoxic effect by reducing the DNA damage activity of nicotine and minimized the percentage of DNA damage (50–60%) in protein restricted dietary condition. The degree of nicotine-induced genotoxicity therefore can be effectively compensated by the protective effect of curcumin in protein stress condition.

BCL6 represses CHEK1 and suppresses DNA damage pathways in normal and malignant B-cells

BCL6 is a transcriptional repressor protein that is expressed in a developmentally regulated fashion during B-cell maturation. Specifically, BCL6 is required for formation of germinal centers in response to T-cell dependent antigen activation. Germinal center B-cells feature the ability to tolerate rapid proliferation and simultaneous genetic recombination. Genetic lesions that cause constitutive expression of BCL6 are commonly associated with diffuse large B-cell lymphomas (DLBCL). Recent studies show that BCL6 contributes to the germinal center phenotype by directly repressing genes involved in sensing or responding to DNA damage including ATR, TP53 and CDKN1A. The CHEK1 protein is activated through phosphorylation by the ATR kinase domain in response to DNA damage. Activated CHEK1 can phosphorylate and modulate the activity a number of proteins including p53, providing a link between ATR sensing of DNA damage and p53 checkpoint activity. Herein we show that BCL6 can directly bind to a DNA consensus element in the CHEK1 promoter and repress its expression in normal and malignant B-cells. DLBCL cells can be killed by a specific BCL6 peptide inhibitor (BPI) that interferes with corepressor binding to the BCL6 BTB domain. BPI could reactivate CHEK1 in DLBCL cells, suggesting that its induction might contribute to BPI anti-lymphoma effects. Therefore, BCL6 can suppress multiple genes involved in a common pathway sensing, transducing and responding to genotoxic stress.

Pioglitazone retrieves hepatic antioxidant DNA repair in a mice model of high fat diet

BackgroundPioglitazone was reported to improve hepatic steatosis and necroinflammation in human studies. To investigate whether the hepato-protective effect of pioglitazone was associated with an improvement of antioxidant defense mechanism, oxidative DNA damage and repair activity were determined in a high fat diet model. Male C57BL/6 mice were respectively fed with a 30% fat diet, the same diet with pioglitazone 100 mg/kg/day, or a chow diet as control for 8 weeks. Tissue oxidative stress was indicated by malondialdehyde concentration. Oxidative DNA damage was detected by immunohistochemical 8-oxoG staining. Enzymatic antioxidant defense was detected by the real-time PCR of superoxide dismutase (Sod1, Sod2) and DNA glycosylase (Ogg1, MutY). Oxidative DNA repair was detected by immunohistochemical staining and western blotting of OGG1 expression.ResultsOur results show that hepatic steatosis was induced by a high-fat diet and improved by adding pioglitazone. Malondialdehyde concentration and 8-oxoG staining were strongly increased in the high-fat diet group, but attenuated by pioglitazone. Gene expressions of antioxidant defense mechanism: Sod1, Sod2, Ogg1 and MutY significantly decreased in the high-fat diet group but reversed by pioglitazone co-administration.ConclusionThe attenuation of hepatic oxidative DNA damage by pioglitazone in a high-fat diet may be mediated by up-regulation of the antioxidant defense mechanism and oxidative DNA repair activity. The diminution of oxidative damage may explain the clinical benefit of pioglitazone treatment in patients with non-alcoholic fatty liver disease.

Alpha - Lipoic Acid Decreases DNA Damage and Oxidative Stress Induced by Alcohol in the Developing Hippocampus and Cerebellum of Rat

Background / aims: The present study was initiated in order to investigate the protective effects of α-lipoic acid upon ethanol-induced DNA damage, lipid peroxidation and protein oxidation in the developing rat hippocampus and cerebellum. Methods: Pregnant Wistar rats received ethanol with, or without lipoic acid from gestation day (GD) 7 throughout lactation. The changes in DNA damage, protein carbonyl, lipid hydroperoxide, catalase and superoxide dismutase activities were measured in the hippocampus and cerebellum of male offspring at the end of the lactation period. Results: The results indicated that DNA damage, lipid peroxidation and protein oxidation in the hippocampus and cerebellum were significantly elevated in animals that received alcohol. However, the catalase and superoxide dismutase activity results showed patterns that differed from those of DNA damage, lipid peroxidation and protein oxidation. Lipoic acid treatment significantly decreased DNA damage compared with the group that were administered alcohol alone, and restored the elevated protein carbonyl and lipid hydroperoxide levels to the levels of the control group. Conclusions: Our findings confirm that oxidative stress and DNA damage occur in the developing hippocampus and cerebellum as a result of alcohol administration, and also suggest that lipoic acid has protective effects as an antioxidant against alcohol-induced disorders in the developing hippocampus and cerebellum.

New method for the detection of reactive oxygen species in anti-tumoural activity of adriamycin: A comparison between hypoxic and normoxic cells

Tumour hypoxia plays a role in chemoresistance in several human tumours. However, how hyperbaric oxygen leads to chemotherapeutic gain is unclear. This study investigates the relation of reactive oxygen species (ROS) generation with anti-tumoural effect of adriamycin (ADR) on CCRF-CEM cells under hypoxic (2% O2) and normoxic (21% O2) conditions. A new method was used to measure intracellular ROS variations through the fluorescence lifetime of 1-pyrenebutyric acid. At 24 h, ADR, probably via semiquinone radical, enhances ROS levels in normoxic cells compared to hypoxic cells. Long-term studies show that ROS are also generated by a second mechanism related to cell functions perturbation. ADR arrests the cell cycle progression both under hypoxia and normoxia, indicating that oxygen and ROS does not influence the DNA damaging activity of ADR. The findings reveal that moderate improvement of ADR cytotoxicity results from higher ROS formation in normoxic cells, leading to elevated induction of cell death.

Sodium selenite enhances glutathione peroxidase activity and DNA strand breaks in hepatoma induced by N-nitrosodiethylamine and promoted by phenobarbital

An element/compound that acts as an antioxidant as well as, can increase the oxidative stress offers a new approach in differentiation therapy. Experiments were carried out to determine the effect of selenite on DNA damage and glutathione peroxidase (GPx) activity in N-nitrosodiethylamine (DEN) induced, phenobarbital promoted rat hepatoma. Supra-nutritional level of selenite (4 ppm) was supplemented at either, before-initiation/after-initiation and/or during entire period of the study. At the end of experiment period (20 weeks), extent of DNA damage (alkaline comet assay), selenium concentration, and GPx activity were assessed on nodular tissue (NL) cells, surrounding liver (SL) cells, and whole liver tissue (control) cells. Hepatic selenium level and GPx activity were decreased in DEN and PB-administered animals, whereas the DNA damage was found to be increased in both NL and SL cells compared with control group. However, the DNA damage is more in SL cells than in NL cells. Pre-supplementation of selenite did not show any difference in DNA (strand breaks) damage, selenium, and GPx activity. Increased hepatic selenium concentration and GPx activity were observed in both NL and SL cells in post-supplementation and entire period of selenite supplemented animals compared to DEN + PB treated animals. However, DNA damage was increased in NL but decreased in SL cells. Supplementation of selenite alone for 16 or 20 weeks had shown increased DNA damage, selenium concentration, and GPx activity compared to normal control animals. In summary, cancer bearing animals increased DNA damage and decreased Se level and GPx activity in NL and SL cells and other organs in cancer bearing animals, supplementation of Se further provoked DNA damage (no change in pretreatment) in NL cells, however it decreased DNA damage SL cells and other organs (kidney, lungs, and spleen). On the other hand Se levels and GPx activity were increased in NL and SL cells and other organs of Se-supplemented rats (no difference in group 3 animals). These results demonstrate that, in addition to chemopreventive and chemotherapeutic role of selenite, it also prevents cellular DNA damage induced in cancerous condition.

DNA-damaging activity and mutagenicity of 16 newly synthesized thiazolo[5,4- a]acridine derivatives with high photo-inducible cytotoxicity

The discovery of the potent anticancer properties of natural alkaloids in the pyrido-thiazolo-acridine series has suggested that thiazolo-acridine derivatives could be of great interest. In a continuous attempt to develop DNA-binding molecules and DNA photo-cleavers, 16 new thiazolo[5,4- a]acridines were synthesized and studied for their photo-inducible DNA-intercalative, cytotoxic and mutagenic activities, by use of the DNA methyl-green bioassay, the Alamar Blue ® viability assay and the Salmonella mutagenicity test using strains TA97a and TA98 with and without metabolic activation and photo-activation. Without photo-activation, one compound showed a DNA-intercalative activity in the DNA major groove while three compounds displayed intercalating properties after photo-activation. In the dark, four molecules possessed cytotoxic activities against a THP1 acute monocytic leukemia cell line while 15 derivatives displayed photo-inducible cytotoxic activity against this cell line. All compounds were mutagenic in strain TA97a with metabolic activation (+S9mix) and 15 molecules were mutagenic in strain TA98 without activation (−S9mix). Study of the quantitative structure–activity relationships (QSAR) from the Salmonella mutagenicity data revealed that several descriptors could describe cytotoxic and mutagenic activities after photo-activation. From the results of the mutagenicity test, four compounds with elevated mutagenic activities were selected for additional experiments. Their capacities to induce single-strand breaks (SSB) and chromosome-damaging effects were monitored by the comet and the micronucleus assays in normal human keratinocytes. Comparison of the minimal genotoxic concentrations showed that two compounds possessed higher capacities to induce SSB after photo-activation. In the micronucleus assay, three molecules were able to induce high numbers of micronuclei following photo-activation. Overall, the results of this study confirm that acridines are predominantly genotoxic via a DNA-intercalating mechanism in the dark, while DNA-adducts were probably induced following photo-activation.

Structure Elucidation of a New Rearranged Abietane Diterpene from a Biologically Active Plant, Salvia eriophora

A new rearranged abietane diterpenoid, eriophoroxide (1), was obtained from the root extract of Salvia eriophora Boiss. and Kotschy ex Boiss. Its structure was elucidated by spectroscopic methods and semi-empirical/ ab-initio calculations. DNA damaging, cytotoxic and antioxidant activities of the plant extract were tested.