DNA repair genes XRCC1 and XRCC3 polymorphisms and their relationship with the level of micronuclei in breast cancer patients

Breast cancer (BC) is the most prevalent type worldwide, besides being one of the most common causes of death among women. It has been suggested that sporadic BC is most likely caused by low-penetrance genes, including those involved in DNA repair mechanisms. Furthermore, the accumulation of DNA damage may contribute to breast carcinogenesis. In the present study, the relationship between two DNA repair genes, viz., XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms, and the levels of chromosome damage detected in 65 untreated BC women and 85 healthy controls, was investigated. Chromosome damage was evaluated through micronucleus assaying, and genotypes determined by PCR-RFLP methodology. The results showed no alteration in the risk of BC and DNA damage brought about by either XRCC1 (Arg399Gln) or XRCC3 (Thr241Met) action in either of the two groups. Nevertheless, on evaluating BC risk in women presenting levels of chromosome damage above the mean, the XRCC3 Thr241Met polymorphism was found to be more frequent in the BC group than in the control, thereby leading to the conclusion that there is a slight association between XRCC3 (241 C/T) genotypes and BC risk in the subgroups with higher levels of chromosome damage.

Genotoxic action of the sesquiterpene lactone Glaucolide B on mammalian cells in vitro and in vivo

O glaucolido B é uma lactona sesquiterpênica, g-lactona a,b-insaturada, isolada da Vernonia eremophila Mart. (Vernonieae, Asteraceae); apresenta atividade esquistossomicida e antimicrobiana, além de atividade analgésica. A aceitaçäo de uma substância para uso medicinal também depende de dados sobre sua toxicidade, além de sua eficiência medicinal. Assim, o objetivo deste trabalho foi testar a atividade clastogênica e citotóxica do composto glaucolido B in vitro e in vivo, utilizando linfócitos em cultura temporária e células da medula óssea de camundongos BALB/c, respectivamente. Analisaram-se o índice mitótico (MI) e as aberraçöes cromossômicas nos sistemas in vitro e in vivo, e trocas entre cromátides irmäs (SCE) e índice proliferativo (PI) somente no ensaio in vitro. Nas culturas de linfócitos humanos as concentraçöes superiores a 15 µg/ml de meio de cultura inibiram totalmente o crescimento celular. Os testes realizados com as concentraçöes 2,4 e 8 µg/ml de meio de cultura demonstraram que o glaucolido B induziu aumento significativo na freqüência de aberraçöes cromossômicas nas culturas tratadas com as duas maiores concentraçöes, e mostrou citotóxico em concentraçöes iguais ou superiores a 8 µg/ml de meio de cultura, mas näo aumentou a freqüência basal de SCE. A análise das células de medula óssea de camundongos näo revelou aumento significativo na freqüência de aberraçöes cromossômicas com a administraçäo de diferentes concentraçöes de glaucolido B (160, 320 e 640 mg/kg de peso corpóreo), e também näo interferiu na divisäo celular. Assim, este composto näo apresentou açäo clastogênica sobre células de mamíferos in vivo, no entanto teve efeito citotóxico e clastogênico in vitro, sendo necessário cautela no seu possível uso como medicamento.

Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in chinese hamster ovary cells

Antioxidantes de ocorrência natural têm sido exaustivamente estudados quanto a sua capacidade de proteger organismos e células contra danos oxidativos. Muitos constituintes das plantas, incluindo cúrcuma e curcumina, parecem ser potentes antimutágenos e antioxidantes. Os efeitos de cúrcuma e curcumina na freqüência de aberraçöes cromossômicas induzidas pelo agente radiomimético bleomicina (BLM) foram investigados em células do ovário de hamster chinês (CHO). Três concentraçöes de cada droga, cúrcuma (100, 250 e 500 mg/ml) e curcumina (2,5, 5,0 e 10 mg/ml), foram combinadas com BLM (10 mg/ml) em células CHO tratadas durante as fases G1/S, S ou G2/S do ciclo celular. Nem cúrcuma nem curcumina evitaram o dano cromossômico induzido pela BLM em fase alguma do ciclo celular. Ao contrário, a potenciaçäo da clastogenicidade da BLM pelo curcumina foi nitidamente observada em células tratadas durante as fases S e G2/S. A curcumina também se mostrou clastogênica na dose de 10 mg/ml nos protocolos de tratamento de 9 e 13 h. Contudo, o mecanismo exato pelo qual a curcumina produziu efeitos potenciadores e clastogênicos permanece desconhecido.

Influence of novobiocin on gama-irradiation G0-lymphocytes as analyzed by cytogenetic endpoints

Experiments with novobiocin (NB) post-treatment were performed to verify its effect on the frequencies of micronuclei (MN) and chromosomal aberrations (CA) induced by g-irradiation (0.75, 1.5 and 3.0 Gy) in human lymphocytes at G0-phase. The frequencies of MN significantly decreased by 44 and 50 per cent, for the treatment with NB 50 µg/ml (30-min pulse) after radiation doses of 1.5 and 3.0 Gy, respectively. However, CA frequencies were not significantly affected. No significant effect on CA was observed when lymphocyte cultures were exposed to a single dose of 2.0 Gy at the G0-phase and posttreated with 25 µg/ml NB for three hours either immediately after irradiation (G0-phase) or after 24 h (S-phase). The significant suppressive effect of NB on MN frequencies supports the hypothesis that NB interaction with chromatin increases access to DNA repair enzymes.

Cytogenetic effects of mebendazole on in vivo and in vitro mammalian systems

Mebendazole (MBZ), (methyl-5 benzoyl benzimidazole-2-carbamate), a potent antihelmintic agent, was tested for clastogenicity in Wistar rat bone marrow cells (l3OO, 1750, 3500 and 7000 mg/kg b.w.) and for both clastogenicity and antimitotic potential in human peripheral blood lymphocytes in culture (5, 10 and 20 mug/ml culture medium). One-hundred metaphases/treatment were analyzed for induction of chromosome aberrations and 2000 cells/treatment were counted to determine the mitotic index. MBZ did not induce an increase in the frequency of chromosome aberrations, however it was effective in blocking the cell cycle at metaphase.

karyotype of ten species of social wasps (Hymenoptera, polistinae, polybiini)

O presente trabalho relata os criótipos das seguintes espécies de vespas sociais da tribo Polybiini: Mischocytarus (Monocytarus) cassununga (n = 32); Mischocytarus sp (n = 34), Metapolybia sp (n = 19); Polybia spl (n = 27); Protopolybia pumila (2n = 42); Protopolybia e. exigua (n = 31) e Parachartergus smithii (2n = 54). Os cromossômicos desta tribo säo discutidos com outras espécies de vespas sociais