In Vitro Cytotoxicity of Nanoparticles in Mammalian Germ-Line Stem Cell

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 1 To whom correspondence should be addressed. E-mail: mpvinardellmh@ ub.edu.