DNA repair pathways and cisplatin resistance: an intimate relationship

The main goal of chemotherapeutic drugs is to induce massive cell death in tumors. Cisplatin is an antitumor drug widely used to treat several types of cancer. Despite its remarkable efficiency, most tumors show intrinsic or acquired drug resistance. The primary biological target of cisplatin is genomic DNA, and it causes a plethora of DNA lesions that block transcription and replication. These cisplatin-induced DNA lesions strongly induce cell death if they are not properly repaired or processed. To counteract cisplatin-induced DNA damage, cells use an intricate network of mechanisms, including DNA damage repair and translesion synthesis. In this review, we describe how cisplatin-induced DNA lesions are repaired or tolerated by cells and focus on the pivotal role of DNA repair and tolerance mechanisms in tumor resistance to cisplatin. In fact, several recent clinical findings have correlated the tumor cell status of DNA repair/translesion synthesis with patient response to cisplatin treatment. Furthermore, these mechanisms provide interesting targets for pharmacological modulation that can increase the efficiency of cisplatin chemotherapy.

Several pathways of hydrogen peroxide action that damage the E. coli genome

Hydrogen peroxide is an important reactive oxygen species (ROS) that arises either during the aerobic respiration process or as a by-product of water radiolysis after exposure to ionizing radiation. The reaction of hydrogen peroxide with transition metals imposes on cells an oxidative stress condition that can result in damage to cell components such as proteins, lipids and principally to DNA, leading to mutagenesis and cell death. Escherichia coli cells are able to deal with these adverse events via DNA repair mechanisms, which enable them to recover their genome integrity. These include base excision repair (BER), nucleotide excision repair (NER) and recombinational repair. Other important defense mechanisms present in Escherichia coli are OxyR and SosRS anti-oxidant inducible pathways, which are elicited by cells to avoid the introduction of oxidative lesions by hydrogen peroxide. This review summarizes the phenomena of lethal synergism between UV irradiation (254 nm) and H2O2, the cross-adaptive response between different classes of genotoxic agents and hydrogen peroxide, and the role of copper ions in the lethal response to H2O2 under low-iron conditions.

Molluscicide activity of the "Avelós" plant (Euphorbia tirucalli, L.) on Biomphalaria glabrata, the mollusc vector of schistosomiasis

Uma soluçäo aquosa de Euphorbia tirucalli (avelós) coletada em locais ensolarados mostrou atividade moluscicida para Biomphalaria glabrata obtendo-se a LD50 a uma concentraçäo de 28,0 ppm e a LD90 a 85,0 ppm. A toxicidade do produto para peixes foi similar a de Bayluscide e sulfato de cobre testados comparativamente. Pela larga distribuiçäo da planta e sua fácil propagaçäo e extraçäo da substância ativa, e pela ausência de efeito residual, a planta pode ser considerada como promissora para testes de campo em locais restritos