teratogenesis

TERATOGENESIS, CARCINOGENESIS & MUTAGENESIS
Vol. 23, issue S1, pp.1-356. 2003

Differential toxic effect of cis-platinum(II) and palladium(II) chlorides complexed with methyl 3,4-diamine-2,3,4,6-tetradeoxy--L-lyxo-hexopyranoside in mouse lymphoma cell lines differing in DSB and NER repair ability  
Marcin Kruszewski 1 2 *, Elzbieta Bouzyk 1, Tomasz Oldak 2, Krystyna Samochocka 2 3, Leon Fuks 1, Wodzimierz Lewandowski 4 5, Izabela Fokt 6, Waldemar Priebe 6  
1Institute of Nuclear Chemistry and Technology, Warsaw, Poland
2Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
3Department of Chemistry, Warsaw University, Warsaw, Poland
4Division of Chemistry, Bialystok Technical University, Bialystok, Poland
5Drug Institute, Warsaw, Poland
6Department of Clinical Investigation, M.D. Anderson Cancer Center of the University of Texas, Houston, Texas  
email: Marcin Kruszewski (marcinkr@orange.ichtj.waw.pl)














*Correspondence to Marcin Kruszewski, Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland
 Funded by:
 State Committee for Scientific Research (KBN, Poland); Grant Number: PO5F 037 15

Keywords
 
L5178Y cells • cis-platin • cytotoxicity • DNA crosslinks • single cell gel electrophoresis • comet assay
 
Abstract
 
The aim of this work was to test the cytotoxicity of newly synthesized cis-type complexes of platinum(II) and palladium(II) dichloride with methyl 3,4-diamine-2,3,4,6-tetradeoxy- -L-lyxohexopyranoside, [M(C7H16N2O2)Cl2]·H2O, against two mouse lymphoma cell lines (L5178Y) differing in their double strand breaks and nucleotide excision repair ability. cis- Diaminedichloroplatinum (CDDP) was used as a reference compound. The toxicity of Pt(C7H16N2O2)Cl2 appeared to be similar for both cell lines: IC50 is 8 µM for L5178Y-R cells and 12 µM for L5178Y-S cells, respectively. In contrast, the palladium complex was found to be more toxic for the LY-R cells than for the LY-S cells. The cytotoxicity of both compounds was compared with their ability to induce DNA crosslinks, as measured by the modified comet assay. CDDP caused retardation of the DNA migration induced by 2 Gy of the X-irradiation in a dose-dependent manner. The ability of Pd(C7H16N2O2)Cl2 to retard X-ray induced DNA migration was more pronounced than its platinum analogue and CDDP (see Fig. 6). However, this was not reflected in the toxicity of the compound. Such results indicate that these two compounds may cause a different type of DNA damage and/or that the DNA damage caused by the palladium(II) compound was dealt with in a different manner from that induced by the platinum(II) complex. Teratogenesis Carcinog. Mutagen. Suppl. 1:1-11, 2003. © 2003 Wiley-Liss, Inc.

 
Differential role of hydrogen peroxide and organic hydroperoxides in augmenting ferric nitrilotriacetate (Fe-NTA)-mediated DNA damage: Implications for carcinogenesis  
Mohammad Iqbal 1 *, Som Datta Sharma 2, Akiko Mizote 1, Masayoshi Fujisawa 1, Shigeru Okada 1  
1Department of Pathological Research, Faculty of Medicine,Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan
2Department of Medical Elementology and Toxicology, Faculty of Science, Hamdard University, New Delhi, India  
email: Mohammad Iqbal (m_iqbal2k@hotmail.com)
*Correspondence to Mohammad Iqbal, Department of Pathological Research, Faculty of Medicine, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-Cho, Okayama 700-8558, Japan
 Funded by:
  Japan Society for the Promotion of Science (JSPS); Grant Number: P01131

Abstract
 
An iron chelate, ferric nitrilotriacetate (Fe-NTA), is a potent nephrotoxic agent, and induces acute and subacute renal proximal tubular necrosis, a consequence of the Fenton-like reaction that eventually leads to a high incidence of renal adenocarcinoma in rodents. In order to examine the possible mechanism for carcinogenic activity, we investigated the DNA damage with Fe-NTA in the presence of various peroxides/organic hydroperoxides. S1 nuclease hydrolysis and deoxyribose degradation assays were performed. Incubation of calf thymus DNA with ferric nitrilotriacetate (0.1 mM) in the presence of peroxides/organic hydroperoxides at a final concentration of 40 mM of each in phosphate buffer (0.1 M, pH 7.4) augmented DNA damage severalfold as compared to the damage caused by individual treatments. Fe-NTA in the presence of hydrogen peroxide caused DNA single-strand breaks and damage to its deoxyribose sugar moiety as measured, respectively, by S1 nuclease hydrolysis and deoxyribose degradation using calf thymus DNA. However, only deoxyribose degradation could be recorded in the presence of other peroxide/organic hydroperoxides. No DNA single-strand break was observed by this treatment. The observed differences in DNA damage by hydrogen peroxide and organic hydroperoxides/peroxide have been ascribed to the differential reactivity of DNA with hydroxyl and alkoxy/aryloxy free radicals produced, respectively, from these inorganic and organic peroxides. These studies suggest that Fe-NTA not only mediated the production of reactive oxygen species, but also catalysed the decomposition of these peroxides and organic hydroperoxides, which may cause a clastogenic change in DNA. This reactivity enhances the clastogenic activity in DNA. These changes in the DNA structure may ultimately be responsible, at least in part, for the induction of carcinogenesis in Fe-NTA-exposed animals. Teratogenesis Carcinog. Mutagen. Suppl. 1:13-21, 2003. © 2003 Wiley-Liss, Inc.


 
Inhibitory effect of Eucommia ulmoides Oliv. on oxidative DNA damage in lymphocytes induced by H2O2  
Gow-Chin Yen *, Chiu-Luan Hsieh  
Department of Food Science, National Chung-Hsing University, Taichung, Taiwan  
email: Gow-Chin Yen (gcyen@mail.nchu.edu.tw)
*Correspondence to Gow-Chin Yen, Department of Food Science, National Chung-Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan
 Funded by:
  Department of Health, Republic of China

Keywords
 
Eucommia ulmoides • DNA damage • comet • lymphocyte • H2O2
 
Abstract
 
This study used the alkaline single cell gel electrophoresis assay (comet assay) to investigate the effect of water extracts of roasted cortex and leaves from Du-zhong on DNA damage in lymphocytes induced by H2O2. The results showed that the DNA damage in human lymphocytes increased with an increase in the concentration of H2O2 (0-200 µ;M), but that the water extracts from Du-zhong (0-2 g l-1) only slightly affected DNA damage. The inhibitory effect of leaf extract on DNA damage induced by H2O2 in lymphocytes was more significant (P<0.05) than that of roasted cortex. Leaf extract showed a rather significant inhibitory effect in a concentration-dependent manner. At a concentration of 2 g l-1, the leaf extract inhibited 37.9% DNA oxidative damage in human lymphocytes. In order to elucidate the mechanism of the leaf extract suppression effect on DNA damage induced by H2O2 in lymphocytes, an experiment was divided with six groups (A-F). Group A was used to evaluate the repair ability of the leaf extract for DNA damage; Group B was employed to determine the scavenging ability on H2O2; and Group C was studied to assess the ability of leaf extract to increase the defense capability. Groups D-F were negative controls and blank. The results showed that group B had the best inhibitory effect. Also, leaf extract had significant ability to scavenge H2O2 in an in vitro HRP-phenol red test. Thus, it appears that H2O2 scavenging potency may be the major mechanism whereby leaf extract inhibits oxidative DNA damage induced by H2O2. Teratogenesis Carcinog. Mutagen. Suppl. 1:23-34, 2003. © 2003 Wiley-Liss, Inc.













 
Expression of aphidicolin-induced fragile sites and their relationship between genetic susceptibility in breast cancer, ovarian cancer, and non-small-cell lung cancer patients  
Varinderpal S. Dhillon 1 *, Syed Akhtar Husain 2, G.N. Ray 2  
1Department of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, Camperdown, Australia
2Department of Biosciences, Jamia Millia Islamia, New Delhi, India  
email: Varinderpal S. Dhillon (dhillonvs@yahoo.com.au)
*Correspondence to Varinderpal S. Dhillon, 12, Shetland Avenue, Marion SA 5043, Australia

 Keywords
 
aphidicolin-induced fragile sites • breast cancer • ovarian cancer • non-small-cell lung cancer • genetic predisposition, chromosome aberrations
 
Abstract
 
Fragile sites are nonrandomly located gaps and/or breaks and their expres-sion can be induced by specific culture conditions. There are many reports in the literature that indicate that these sites can act as factors that predispose to specific chromosome aberrations and other complex rearrangement in the chromosome and their association with cancers. In the present study, the expression of the fragile sites induced by aphidicolin was evaluated on prometaphase chromosomes from peripheral blood lymphocytes of 55 patients with breast cancer patients belonging to different stages of the cancer, 25 patients with epithelial ovarian cancer, and 13 with non-small-cell lung cancer, 100 of their first-degree clinically healthy female relatives, and 100 normal age-matched healthy persons without a familial history of cancer. The frequency of expression of the fragile sites in cancer patients and their first-degree relatives was found to be statistically significant (P<0.05) than those of the controls. In different stages of breast cancer patients, 6q26 is the best-defined fragile site whereas 13q13 is confined to stage II and stage III patients only. The chromosomal aberration rate/cell in breast cancer patients was found to be 0.29±0.13, in epithelial ovarian cancer patients 0.38±0.14, and in non-small-cell lung cancer 0.29±0.11 as compared to 0.07±0.03 in controls, and was found to be statistically significant. Therefore, our results indicate that these fragile sites may be the unstable sites in the genome and, hence, can be used as suitable and reliable markers for genetic predisposition to breast cancer, epithelial ovarian cancer, and in non-small-cell lung cancer. Teratogenesis Carcinog. Mutagen. Suppl. 1:35-45, 2003. © 2003 Wiley-Liss, Inc.








 
Mutant spectra analysis at hisG46 in Salmonella typhimurium strain YG1029 induced by mammalian S9- and plant-activated aromatic amines  
Young H. Ju 1 *, Michael J. Plewa 2  
1Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois
2Department of Crop Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois  
email: Young H. Ju (yhju@uiuc.edu)
*Correspondence to Young H. Ju, 574 Bevier Hall, Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign, 905 South Goodwin Avenue, Urbana, IL 61801
 Funded by:
  U.S. Environmental Agency; Grant Number: R-823184

Keywords
 
Salmonella • mutation spectra • hisG46 • Salmonella typhimurium • YG1029 • plant-activation • S9-activation • benzidine • 4-aminobiphenyl
 
Abstract
 
Mutant spectra analysis was conducted with spontaneous hisG46 revertants of Salmonella typhimurium strain YG1029 and revertants induced by the plant- and mammalian S9-activation of benzidine and 4-aminobiphenyl (4-ABP). Under preincubation conditions, YG1029 cells were exposed to benizidine or 4-ABP with mammalian S9 activation or to a high molecular weight fraction that contained the plant-activated products. The induced revertants were isolated at mutagen concentrations that caused an increased mutant frequency of approximately 4- to 10-fold above background. Genomic DNA from each revertant was isolated and the hisG region was amplified using polymerase chain reaction (PCR). Using a series of specific probes and a modified version of the ECL3's-oligolabelling and detection system, each of the six possible base-pair substitution mutations at hisG46 that leads to a reversion event was determined. Of the YG1029 spontaneous revertants, transition mutations were 31.8% and transversion mutations were 68.2%. The YG1029 spontaneous mutant spectrum differed significantly from the spontaneous spectrum of TA1535 but did not significantly differ from the spontaneous TA100 mutant spectrum. The differences of the spontaneous mutant spectra among these highly related strains illustrate that the introduction of the plasmid pKM101 into S. typhimurium increased the frequency of transversions (CCC ACC; CCC CAC) and reduced site 2 (CCC CTC) transitions. With plant-activated benzidine, 21.1% of recovered revertants resulted from transitions and 78.9% from transversions while S9 activated-benzidine induced revertants were recovered as 14.2% from transition and 85.8% from transversion mutations. Plant-activated 4-ABP recovered 20.0% transitions and 80.0% transversions. S9-activated 4-ABP-induced 21.4% transitions and 78.6% transversions. Chi-square analysis of mutant spectra indicated that the DNA lesions that resulted in reversion at the hisG46 allele induced by plant-activated benzidine or 4-ABP were different from those generated after mammalian S9 activation of these promutagens. The plant-activated benzidine and 4-ABP induced statistically identical mutant spectra. Also, the mammalian-activated benzidine and 4-ABP induced statistically similar mutant spectra. These data show that the plant-activated and mammalian-activated aromatic amine products inflicted different types or distributions of DNA lesions that were reflected in the resulting induced mutant spectra. Teratogenesis Carcinog. Mutagen. Suppl. 1:47-60, 2003. © 2003 Wiley-Liss, Inc.
 
Rat breast microsomal biotransformation of ethanol to acetaldehyde but not to free radicals: Its potential role in the association between alcohol drinking and breast tumor promotion  
G.D. Castro, A.M.A. Delgado de Layño, M.H. Costantini, J.A. Castro *  
Centro de Investigaciones Toxicológicas (CEITOX)-CITEFA/CONICET, Buenos Aires, Argentina  
email: G.D. Castro (postmast@ceitox.edu.ar)
*Correspondence to J.A. Castro, CEITOX-CITEFA/CONICET, J.B. de La Salle 4397, B1603ALO Villa Martelli, Buenos Aires, Argentina
 Funded by:
  Agencia de Promoción Científica y Tecnológica, Argentina

Keywords
 
breast cancer and alcohol drinking • breast biotransformation of alcohol • acetaldehyde and breast cancer
 
Abstract
 
We recently showed that mammary cytosolic xanthineoxidoreductase had the ability to bioactivate ethanol (EtOH) to acetaldehyde (AC) and free radicals. In the present study, we report that the microsomal fraction also biotransforms EtOH to AC. One pathway requires NADPH and the others do not. Both need oxygen. The NADPH-dependent pathway is not inhibited by CO:O2 (80:20) or SKF 525A and that excludes the participation of cytochrome P450. It is inhibited by diethyldithiocarbamate (DDTC), sodium azide, and diphenyleneiodonium (DPI) but not by desferrioxamine, which suggests a possible role of a non-iron copper-requiring flavoenzyme. The process was partially inhibited by thiobenzamide (TBA), methylmercaptoimidazole (MMI), and nordihydroguaiaretic acid (NDG) but not by dapsone, aminotriazole, or indomethacin. These results suggest the potential participation of flavine monooxygenase and of lipooxygenase or of peroxidases/oxidases having similar characteristics but not of lactoperoxidase or cyclooxygenase. The pathway not requiring NADPH could also be partially inhibited by DDTC, NDG, azide, DPI, and TBA or MMI but not by the other chemicals. Little activity proceeds under nitrogen. Oxidases or peroxidases might be involved. No formation of 1-hydroxyethyl radicals was detected either in the presence or absence of NADPH. The nature of the EtOH bioactivating enzymes involved remains to be established. However, the fact remains that an activation of EtOH to AC was found in mammary tissue and could have a significant effect in some stages of the process of breast tumor promotion by EtOH. Teratogenesis Carcinog. Mutagen. Suppl. 1:61-70, 2003. © 2003 Wiley-Liss, Inc.






 
Natural dietary agents can protect against DMBA genotoxicity in lymphocytes as revealed by single cell gel electrophoresis assay  
Sarmishtha De, Chaiti Ganguly, Sukta Das *  
Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India  
email: Sukta Das (sukta2002@hotmail.com)
*Correspondence to Sukta Das, Dept. of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata - 7000 26, India

 Keywords
 
alpha tocopherol • quercetin • bitter gourd • tomato • DMBA genotoxicity • comet assay
 
Abstract
 
Many natural agents including fruits and vegetables are known to provide protection from different degenerative diseases including cancer, by preventing damage to the cellular components. The effect of two important dietary agents, alpha tocopherol, and the flavonoid quercetin, along with two commonly consumed vegetables, bitter gourd and tomato, were investigated on spontaneous and dimethylbenz(a)anthracene (DMBA)-induced DNA damage in murine lymphocytes in vitro. DNA damage was determined by single cell gel electrophoresis (comet assay). The rationale for such an approach for this study is that DNA damage can lead to genetic disorders that occur at different stages of carcinogenesis and protection from such damages may in the long run help to prevent development of cancer. Both alpha tocopherol and quercetin as single agents were found to be potent inhibitors of DNA damage (spontaneous and carcinogen induced) in a dose-dependent manner. Fresh juices of bitter gourd and tomato could also protect from DMBA-induced DNA damage but not as effectively as the single agents. The anticarcinogenic role of nutrients as well as non-nutrient dietary components need to be explored more extensively. The Comet assay is a simple, fast, and reliable method to determine the protective effect against DNA damage, one of the prerequisites for carcinogenesis. Teratogenesis Carcinog. Mutagen. Suppl. 1:71-78, 2003. © 2003 Wiley-Liss, Inc.













 
Induction of DNA damage in human lymphocytes treated with a soluble factor secreted by Taenia solium metacestodes  
Luis A. Herrera 1 2 *, Patricia Tato 3, José L. Molinari 4, Enrique Pérez 2, Hugo Domínguez 2, Patricia Ostrosky-Wegman 1  
1Instituto de Investigaciones Biomédicas, UNAM, Ciudad Universitaria, México D.F., México
2Instituto Nacional de Cancerología, SSa, México D.F., México
3Facultad de Medicina, UNAM, Ciudad Universitaria, México D.F., México
4Instituto de Fisiología Celular, UNAM, Ciudad Universitaria, México D.F., México  
email: Luis A. Herrera (metil@hotmail.com)
*Correspondence to Luis A. Herrera, Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, UNAM. P.O. Box 70-228, Ciudad Universitaria, México D.F., 04510, México

 Keywords
 
cysticercosis • neurocysticercosis • parasites • cancer • micronucleus
 
Abstract
 
We have previously reported that a factor secreted by the metacestode of Taenia solium (MF) is able to transform Syrian hamster embryo cells. The aim of this study was to analyze the genotoxicity of MF in cultured human lymphocytes using the micronucleus assay. Results show a significantly high frequency of micronucleated cells in lymphocyte cultures treated with MF. Although further experiments are needed to determine whether this factor is also secreted by T. solium metacestodes in humans, analysis of the frequency of micronucleus induced in cultured human lymphocytes indicates that DNA instability induced by MF could represent a risk for malignant transformation. Teratogenesis Carcinog. Mutagen. Suppl. 1:79-83, 2003. © 2003 Wiley-Liss, Inc.




















 
Antiperoxidative, anti-inflammatory, and antimutagenic activities of ethanol extract of the mycelium of Ganoderma lucidum occurring in South India  
B. Lakshmi, T. A. Ajith, N. Sheena, Nidhi Gunapalan, K. K. Janardhanan *  
Amala Cancer Research Centre, Thrissur, Kerala, India  
email: K. K. Janardhanan (kkjanardhanan@yahoo.com)
*Correspondence to K. K. Janardhanan, Amala Cancer Research Centre, Amala Nagar, Thrissur 680 553, Kerala, India
 Funded by:
  Council of Scientific and Industrial Research (CSIR), New Delhi

Keywords
 
Ganoderma lucidum • mycelium • antiperoxidation • antiinflammation • antimutagenicity
 
Abstract
 
Free radical mediated genetic instability is widely thought to be a major etiological factor for initiation of carcinogenesis. Mushrooms represent a largely untapped source of powerful new pharmaceutical products. In the present study, we examined the antiperoxidative, anti-inflammatory, and antimutagenic activities of the ethanol extract of the mycelium of a medicinal mushroom, Ganoderma lucidum, occurring in south India. Antiperoxidative activity was evaluated using Fe2+-ascorbate-induced lipid peroxidation in rat liver homogenate and a phorbol ester (croton oil)-induced lipid peroxidation in mouse skin. Antiinflammatory activity was evaluated against carrageenan-induced acute and formalin-induced chronic inflammatory paw edema in mouse and phorbol ester-induced mouse skin inflammation. Antimutagenic activity was determined by the Ames mutagenicity assay using histidine mutant of Salmonella typhimurium strains TA 98, TA100, and TA102. Sodium azide (NaN3), N-methyl-N-nitro-N-nitrosoguanidine (MNNG), 4-nitro-o-phenylenediamine (NPD), and benzo[a]pyrene (B[a]P) were used as the mutagens. The extract showed significant inhibition of Fe2+-induced peroxidation of lipid in rat liver (IC50 510 ± 22 µg/ml) and 37% inhibition of croton oil-induced peroxidation on the mouse skin at 20 mg/0.1 ml/skin. Carrageenan-induced acute and formalin-induced chronic inflammatory edema were inhibited by 56 and 60%, respectively, by the extract at 1,000 mg/kg body wt (i.p). The extract at a concentration of 5 mg/plate showed inhibition of mutagenicity elicited by direct acting mutagens, NaN3 (55.5 and 75.7%) and MNNG (50.0 and 57.5%) for S. typhymurium strains TA100 and TA102, respectively. The extract at the same concentration also inhibited mutagenicity elicited by NPD (52.4 and 64.2%) and B[a]P (60.7 and 59.6%) for TA98 and TA100 strains, respectively. The B[a]P was activated in the presence of rat liver microsomal (S9) fraction. The results of our study revealed that ethanol extract of Ganoderma lucidum mycelium possessed significant antiperoxidative, antiinflammatory, and antimutagenic activities. The findings suggest a medicinal use for the ethanol extract of the mycelium of G. lucidum occurring in South India. Teratogenesis Carcinog. Mutagen. Suppl. 1:85-97, 2003. © 2003 Wiley-Liss, Inc.


 
Ascorbic acid potentiates mitomycin C-induced micronuclei and sister chromatid exchanges in human peripheral blood lymphocytes in vitro  
A.P. Krishnaja *, N.K. Sharma  
Genetic Toxicology and Chromosome Studies Section, Cell Biology Division, Bhabha Atomic Research Centre, Mumbai, India  
email: A.P. Krishnaja (krishnja@apsara.barc.ernet.in)
*Correspondence to A.P. Krishnaja, Genetic Toxicology and Chromosome Studies Section, Cell Biology Division, Bhabha Atomic Research Centre, Mumbai, 400 085, India

 Keywords
 
vitamin C • antineoplastic agent • chromosome damage • genotoxicity • human lymphocytes • sister chromatid exchanges • micronuclei • CBMN assay
 
Abstract
 
Vitamin C (l-ascorbic acid), an effective free radical scavenger present as ascorbate in most biological systems, is one of the most extensively studied antioxidant vitamins. Vitamin C acts as either a free radical scavenger or a pro-oxidant producing hydrogen peroxide and free radicals. The modulatory effect of L-ascorbic acid (AA) on Mitomycin C (MMC) induced chromosome damage has been evaluated in human peripheral blood lymphocytes in vitro. The effect of L-ascorbic acid, 200 µg/ml as 1- and 2-h pretreatment on the frequencies of the biomarkers micronuclei (MN), sister chromatid exchanges (SCEs), and chromosome aberrations (CA) induced by mitomycin C 0.1 and 0.2 µg/ml has been studied. AA pretreatment caused a statistically significant increase in MMC-induced MN and SCE frequencies for all treatment groups, but did not show an increase in induced chromosome aberrations compared to MMC treatment alone. Cell division delays caused by MMC was reversed in the presence of AA. Interindividual variability in MMC as well as AA plus MMC-induced MN, SCE, and CA frequencies were evident. Ascorbic acid potentiated MMC-induced chromosome damage in human lymphocytes in vitro. The potentiation observed has to be viewed in the light of metal ion catalysed autooxidation of AA in oxygenated media and the existence of an antioxidant system in vivo that inactivates oxyradicals before their interaction with DNA. Teratogenesis Carcinog. Mutagen. Suppl. 1:99-112, 2003. © 2003 Wiley-Liss, Inc.










 
Repair of 8 oxoguanine in mammalian cells expressing the Drosophila S3 ribosomal/repair protein  
Enrico Cappelli 1, Andrea D'Osualdo 1, Massimo Bogliolo 1, Yi Xu 2, Mark R. Kelley 2, Guido Frosina 1 *  
1DNA Repair Unit, Mutagenesis Laboratory, Istituto Nazionale Ricerca Cancro, Genova, Italy
2Department of Pediatrics and Biochemistry and Molecular Biology, Herman B. Wells Center for Pediatric Research, Indiana University Medical School, Indianapolis, Indiana  
email: Guido Frosina (guido.frosina@ istge.it)
*Correspondence to Guido Frosina, DNA Repair Unit, Mutagenesis laboratory, Istituto Nazionale Ricerca Cancro, Largo Rosanna Benzi n. 10, 16132 Genova, Italy
 Funded by:
  Compagnia di San Paolo
  Italian Association for Cancer Research (AIRC)
  Ministry of University and Research, Strategic Programme  Post Genoma.

Abstract
 
8-oxo-7,8-dihydroguanine (8-oxoG) is a potent mutagenic lesion that forms at elevated levels in cellular DNA and is repaired with low efficiency in human cells. Unlike its human counterpart, the Drosophila S3 ribosomal/repair protein is endowed with a vigorous 8 oxoG repair activity that is associated to  , -elimination AP lyase activity. We have recently observed that pure GST-tagged Drosophila S3 protein can significantly accelerate the in vitro repair of 8 oxoG performed by human and mouse cell extracts [Cappelli et al., unpublished data]. In this work, we have transfected Chinese hamster cells with mammalian expression vectors containing the Drosophila S3 cDNA. The cells synthesized both S3 mRNA and protein but no improved repair of 8 oxoguanine was observed. Factors important for the proper expression of Drosophila genes in mammalian cells are discussed. Teratogenesis Carcinog. Mutagen. Suppl. 1:113-121, 2003. © 2003 Wiley-Liss, Inc.


pp.113-121