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«Nanocorpuscular mutagenesis: New horizons» 
S.T. Zakhidov

Rapid development of nanotechnologies in the nearest future may shape the third stage in the experimental research into mutational hereditary variability. It will involve the emergence of a new special research field in genetics, nanocorpuscular mutagenesis that implies the process of inducing genetic changes by nanoparticles and/or nanostructured materials.

In its importance and intensity of its effects, diversity and range of induced mutations, nanocorpuscular mutagenesis will probably be on a par with chemical and radiation mutagenesis that has been helping to tackle numerous problems of modern genetics and selection over many years. Indeed, the bulk of data concerning chemical and radiation mutagenesis is immense. This data indicates that the methodology of induced experimental mutagenesis provides a powerful means of acting on living systems and may often produce positive results. In most cases, preference is given to chemical mutagens and supermutagens that have been shown to increase mutation frequency in plants by two or three orders of magnitude and in microorganisms by four or five orders of magnitude, compared to spontaneous mutagenesis levels [1]). It is also known that molecular mutagens may help to identify genes on the chromosomes, induce profound changes in the metabolic and genetic processes, and, hence, speed up the development of new forms and selection processes, mobilize hidden genetic resources that may help to enhance major crop varieties’ productivity, increase survival and fecundity rates, and eradicate tumors. On the other hand, molecular mutagens may reduce fat and protein content in milk, wool production in sheep, or the content of silk in silkworm cocoons that have been developed excessively in the course of artificial selection.

A possibility cannot be ruled out that genetically active (nano)substances synthesized using nanotechnology methods will be found to possess properties that have not been known to exist in chemical and radiation mutagens. One may expect that nanomutagens will easily, without significant energy costs, penetrate through the surface and intracellular barriers, minimizing overall toxicity; have less aggressive and more profound effects on act on the genetic apparatus; target the harmful, deadly genes, and realize the constructive potential of mute genes and pseudogenes. Nanomutagens are likely to enable obtaining the new types of the positive, progressive (nano)mutations, overcoming some ontogenetic and evolutionary taboos, and glimpse into the evolutionary past or the uncertain future.

Nanomutagens may become an important tool for discovering the fundamentally new mechanisms underpinning changes in the structure of genetic material.

Nanomutagens are sure to help to identify new genetic patterns and tackle a number of both the specialized and general biological problems, including those economically important. E.g. using nanomutagens in mutational selection practices may open new possibilities for creating new unique varieties of crop plants and livestock breeds, more flexible and viable, more fecund and productive.

On the other hand, some types of metal nanoparticles may have strong effects on the viral and bacterial genes which, in contrast to host cell genes, are extremely sensitive to inorganic compounds. It must not be ruled out that the viruses and bacteria that have mutated as result of exposure to genetically active nanoparticles will bring unexpected surprises.
And, finally, it should be mentioned that the widespread introduction of nanotechnology products into industrial manufacturing, biotechnology and practical medicine will set an additional task for the modern mutational genetics whose experimental interests will gradually refocus from the chemical and radiation mutagenesis to nanocorpuscular mutagenesis. This additional task is assessment of genetic risks of engineered nanosubstances, first and foremost, drugs and drug delivery agents. We do not know yet the organic and inorganic nanoparticles’ affinity for genes and chromosomes, and their effects on the key genetic processes such as replication, transcription, and reparation. However, there is evidence in the literature suggesting that nanoparticles can excite the DNA molecule, disturb its spatial packaging, cause single- and double-strand DNA breaks, point mutations and severe chromosome defects, as well as morphological abnormalities in the subsequent generations [2, 3, 4, 5, 6, 7, 8, 9, 10]. The Italian scientists have recently demonstrated the first nano-mutants in the experiments with Drosophila: the progeny arising from the organisms treated with gold nanoparticles had deformed eyes, wings, and thorax [10]. I.A.Rapoport had pointed out to the fact that [11], every time a mutagen was discovered to be active in chemical experiments with Drosophila, it was also found to be active in many other organisms. Our pilot studies using murine male germ cells demonstrated that ultrasmall gold nanoparticles may play three different roles, depending on the experimental conditions: that of a mutagen, antimutagen, or comutagen [12]. All these, so far scanty facts should be taken into account by professionals engaged in nanotechnology developments.

Thus, in the long term, nanocorpuscular mutagenesis will provide a new experimental basis for a deeper understanding of living systems’ development processes and for obtaining fundamentally new artificial life forms, and will thus expand the scope for the geneticists and biologists, biotechnologists and medical specialists. As regards the problem of genetic safety of materials obtained using nanotechnological synthesis, it will probably require the years-long, laborious genetic studies to tackle it successfully. In the modern context, only such studies may set up the barrier for the release of genetically hazardous nanomaterials into the environment.


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