TY - JOUR
AU - Vinardell, Maria, Pilar
AB - Nanotechnology involves the creation and manipulation of materials at nanoscale levels to create products that exhibit novel properties. There are important applications of nanoscience in biology and biotechnology, and nanotechnology offers new tools to biologists (Whitesides, 2003). Nevertheless, despite the increased interest in the development of nanoparticles, few studies address their potential toxicity. The rapidly developing field of nanotechnology is likely to become yet another source of human exposure to nanoparticles by different routes: inhalation, ingestion, dermal, and injection. Regulatory agencies, researchers, and health and environmental watchdogs are assessing how nanoscale materials affect human health and the environment (Service, 2004). Similarly, the characteristic biokinetic behavior of nanoparticles is an attractive quality for promising applications in medicine. Such applications include diagnostic and therapeutic devices and tools to investigate and understand molecular processes and structures in living cells However, in stark contrast to the many efforts aimed at exploiting the desirable properties of nanoparticles for improving human health, attempts to evaluate potential undesirable effects when administered for medical purposes or after exposure during manufacture or processing for industrial applications are limited. Nanotoxicology, an emerging discipline, is gaining increased attention. Nanotoxicology research will not only provide data for safety evaluation of engineered nanostructures and devices, but will also help to advance the field of nanomedicine by providing information about their undesirable properties and means to avoid them (Oberdörster et al., 2005). The safety and toxicity of nanoparticles are of growing concern despite their significant scientific interest and promising potential in many applications. Their biological activity and biokinetics are dependent on many parameters: size, shape, chemistry, charge, surface modifications, etc. When inhaled, they can translocate out of the respiratory tract via different pathways and mechanisms. When ingested, systemic uptake of nanoparticles via lymph can occur. When in blood circulation, they can distribute throughout the organism, and they are taken up by liver, spleen, bone marrow, heart, and other organs such as testis. The study of the toxic effect of nanoparticles on gametogenesis is of great interest. The identification of toxic properties of new compounds at an early stage has a high priority before human or animal testing in vivo can begin. Because adverse effects on reproduction are among the most hazardous side effects of drugs and chemicals, there is an increasing demand for new in vitro models that can be used for selecting lead chemicals in drug development. All new chemical and pharmaceutical products are tested before humans are exposed to them, either intentionally or accidentally, in order to evaluate any potential hazard associated with such exposure. To determine the magnitude and target of any toxicity, tests are carried out in animals and, subsequently, in humans. Many of these tests are required by national and international regulatory authorities. New compounds are tested, for specific ethical and regulatory reasons, to identify possible adverse effects and mechanisms of toxicity. It is widely recognized that there is a need to improve the current testing methods to maximize the relevance of the information generated with respect to the prediction of adverse effects in humans. Several in vivo animal models have been used to assess the testicular toxicity of many compounds. These models entail the sacrifice of animals and the determination of different enzymes, sperm motility, and testis morphology (Haffor et al., 2004; Kuriyama et al., 2005). To avoid testing in several species of animals in vitro, systems that provide information on species-specific metabolism, pharmacokinetics, and toxicology are essential. It is clear that the full potential of alternative approaches in toxicological risk assessment has yet to be fully realized. For instance, the application of a new chemical to cultured cells derived from a particular tissue permits the determination of the concentration of that chemical at which a certain effect occurs in that cell type. This sometimes leads to knowledge of the fundamental mechanisms underlying the toxic effect, but it does not yield the full profile of toxic effects caused by the chemical in the intact organism. Alternatively, a number of studies have attempted to combine the use of a variety of methods (Blaauboer et al., 1999). Criticism of the use of laboratory animals for the safety testing of chemicals is increasing, in society as a whole and also in the scientific world. This criticism is not only limited to ethical concerns, but scientific considerations also play a significant role. It should be realized that the animal bioassays presently used in toxicity testing are model systems for the prediction of toxicity in humans or the environment. In the last few decades new technologies and new knowledge have become available. This development is the result of intensive fundamental toxicological research and the implementation of new methods and technologies (Gubbels-van Hal et al., 2005). The development of in vitro models of testicular toxicity may provide important tools for investigating specific mechanisms of toxicity in the testis. Although various systems have been reported, their application in toxicological studies has been limited by the poor ability to replicate the complex biochemical, molecular, and functional interactions observed in the testis. In vitro models have been established, and some of them have tried to reproduce the complex interactions that take place between the different germ cells. These models are limited by the poor viability of freshly isolated germ cells. So the development of a germ-line stem cell is of great interest. After previous studies to develop an immortalized cell line (Hofmann et al., 1992), the authors finally obtained a cell line (Hofmann et al., 2005) with promising application in the study of testis toxicity. The highlighted article reports the efficacy of the new stem cell line C18-4 in testing cytotoxicity and the possibility of studying the molecular mechanism of nanoparticle toxicity in future studies. The authors open the way to studying this mechanism in this cell line. To study the early phases of spermatogenesis at the molecular level, an in vitro system must be devised whereby germ line stem cells can be either cultured for a prolonged period or expanded as cell lines (Hofman et al., 2005a,b). The development of alternative in vitro methods to study the toxicity of new compounds is of great interest, and the establishment of a new cell line in which to study reproductive toxicity constitutes an important field of research due to the advantages over other cell cultures. The study by Braydich-Stolle et al. describes the application of germ line stem cells to the study of the toxicity of nanoparticles and increases our knowledge of the toxicological effect of nanoparticles. References Blaauboer, B. J., Barratt, M. D., and Houston, J. B. ( 1999 ). The integrated use of alternative methods in toxicological risk evaluation. ATLA, 27, 229 –237. Gubbels-van Hal, W. M. L. G., Blaauboer, B. J., Barentsen, H. M., Hoitink, M. A., Meerts, I. A. T. M., and van der Hoeven, J. C. M. ( 2005 ). An alternative approach for the safety evaluation of new and existing chemicals, an exercise in integrated testing. Reg. Toxicol. Pharmacol. 42, 284 –295. Haffor, A. S., and Abou-Tarboush, F. M. ( 2004 ). Testicular cellular toxicity of cadmium: Transmission electron microscopy examination. J Environ. Biol. 25, 251 –258. Hofmann, M. C., Braydich-Stolle, L., Dettin, L., Johnson, E., and Dym, M. ( 2005 a). Immortalization of mouse germ line stem cells. Stem Cells 23, 200 –210. Hofmann, M. C., Braydich-Stolle, L., and Dym, M. ( 2005 b). Isolation of male germ-line stem cells; influence of GDNF. Dev. Biol. 279, 114 –124. Hofman, M. C., Narizawa, S., Hess, R. A., and Millan, J. L. ( 1992 ). Immortalization of germ cells and somatic testicular cells using the SV40 large antigen. Exp. Cell. Res. 201, 417 –435. Hussain, S. M., Hess, K. L., Gearhart, J. M., Geiss, K. T., and Schalager, J. J. ( 2005 ). In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol. In Vitro (In press). Kuriyama, K., Yokoi, R., Kobayashi, K., Suda, S., Hayashi, M., Ozawa, S., Kuroda, J., and Tsujii, H. ( 2005 ). A time-course characterization of male reproductive toxicity in rats treated with methyl methanesulphonate (MMS). J. Toxicol. Sci. 30, 91 –102. Oberdörster, G., Oberdörster, E., and Oberdörster, J. ( 2005 ). Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 223, 823 –839. Seiler, A., Visan, A., Buesen, R., Genschow, E., and Spilelman, H. ( 2004 ). Improvement of an in vitro stem cell assay for developmental toxicity: The use of molecular endpoints in the embryonic stem cell test. Reprod. Toxicol. 18, 232 –240. Service, R. F. ( 2004 ). Nanotechnology grows up. Science 304, 1732 –1734. Whitesides, G. M. ( 2003 ). The right size in nanobiotechnology. Nat. Biotechnol. 21, 1161 –1164. © The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
TI - In Vitro Cytotoxicity of Nanoparticles in Mammalian Germ-Line Stem Cell
JF - Toxicological Sciences
DO - 10.1093/toxsci/kfi340
DA - 2005-12-01
UR - https://www.deepdyve.com/lp/oxford-university-press/in-vitro-cytotoxicity-of-nanoparticles-in-mammalian-germ-line-stem-TosOv83cTi
SP - 285
EP - 286
VL - 88
IS - 2
DP - DeepDyve
ER -