Novi aspekti u klasifikaciji kancerogena

The existing systems of classification of carcinogens should include a distinction between genotoxic and non-genotoxic chemicals. For non-genotoxic chemicals, permissible exposure levels can be derived at which no relevant human cancer risks are anticipated. While genotoxic carcinogens can induce chromosomal effects without mutagenic action, non-DNA-reactive genotoxins affecting topoisomerase or the spindle, or those having an exclusively aneugenic effect can be carcinogenic only at high, toxic doses. Specific mechanisms of clastogenicity and processes of carcinogenesis based on reactive oxygen have practical thresholds. Since reactive oxygen species (ROS) are generally genotoxic, the question is whether chemicals that increase ROS production will add to endogenously produced background levels and lead to nonlinear dose-effect relationships. Taking into account the presence of endogenous carcinogens, it is now becoming evident that carcinogenic risk extrapolation to low doses must be considered according to the mode of action.U postojećem sistemu klasifikacije kancerogenih tvari utvrđena je razlika između genotoksičnih i negenotoksičnih kemikalija. Za negenotoksične kemikallije mogu se izvesti pretpostavljeni stupnjevi izlaganja kod kojih ne postoji značajan rizik od pojave raka kod ljudi. Za genotoksične kancerogene mogući su na primjer inducirani kromosomski efekti bez početka procesa mutageneze, dok genotoksični toksini koji se ne vežu za DNA-molekulu, a djeluju na topoizomere ili diobeno vreteno ili su aneugeni, izazivaju kancerogene efekte jedino u visokim, toksičnim dozama. Za specifične mehanizme klastrogenog djelovanja i procesa kancerogeneze koji se baziraju na reaktivnom kisiku postoji prag početka procesa. Kako su vrste kemikalija reaktivne na kisik (ROS) u načelu genotoksične, pojavljuju se pitanja da li kemikalije koje povećavaju produkciju ROS-vrsta treba pridodati endogenim kancerogenima pozadinskog stupnja koji uzrokuju nelinearni odnos doze i učinka. Uzimajući u obzir rasprave o prisutnosti endogenih kancerogena, sada postaje jasno da se kancerogeni rizik od niskih doza mora uzeti u obzir sukladno načinu njihova djelovanja

The influence of glutathione S­-transferases M1 and M3 on the development of bladder cancer

Problem: Cigarette smoking is the most important risk factor of transitional cell carcinoma of the urinary bladder. The effect of the glutathione S­transferases M1 (GSTM1) and M3 (GSTM3) on the influence of this risk factor was investigated. Methods: A total of 293 bladder cancer patients from Dortmund and Wittenberg as well as 176 surgical patients without any malignancy from Dortmund were genotyped for GSTM1 und GSTM3 according to standard PCR/RFLP methods. Smoking habits were also qualified by a standardized interview. Results: The percentage of GSTM1 negative cases was 63 % in the entire bladder cancer patient group compared to 50 % in the control group. GSTM3*A/*A genotype was 76 % in the entire group of bladder cancer cases and 74 % in controls. Smokers and ex­smokers were overrepresented in the bladder cancer patient group. A significant association between smoking status and GSTM1 or GSTM3 genotype could not be revealed. Conclusion: The elevated percentage of GSTM1 negative bladder cancer cases shows the important effect of this polymorphic enzyme on the development of bladder cancer. In contrast to some other studies, an influence of GSTM1 on the risk due to cigarette smoking could not be observed

Ceramic/metal nanocomposites by lyophilization: Processing and HRTEM study

5 páginas, 8 figuras, 1 tabla.-- El pdf del artículo es el manuscrito de autor.This work describes a wet-processing route based on spray-freezing and subsequent lyophilization designed to obtain nanostructured ceramic/metal powders. Starting from the ceramic powder and the corresponding metal salt, a water-based suspension is sprayed on liquid nitrogen. The frozen powders are subsequently freeze-dried, calcined and reduced. The material was analyzed using X-ray diffraction analysis at all stages. High resolution transmission electron microscopy studies showed a uniform distribution of metal nanoparticles on the ceramic grain surfaces, good interfaces and high crystallinity, with an average metal particle size in the nanometric range.This work was supported by the Spanish Ministry of Science and Innovation (MICINN) under the project MAT2009-14542-C02 and the Government of the Principality of Asturias through PCTI and ERDF (European Regional Development Fund) 2007-2013 under project PC10-65. C.F. Gutierrez- Gonzalez acknowledges CSIC and ESF for the concession of a JAE-Doc 2009 grant. S. Agouram thanks the Spanish Ministry of Science and European Social Fund for financial support.Peer reviewe