V.B. Popov
G.A. Protasova |
THE COMPLEX ASSESSMENT OF HUMAN BLOOD PATHOGENIC FACTORS, INDUCED BY CHEMICALS,
DRUGS AND UNFAVORABLE ENVIRONMENTS |
| Federal State Unitary «Research Institute of Hygiene, Occupational Pathology
and Human Ecology» Federal Medical Biological Agency, Saint Petersburg,
Russia |
The preventive medicine based on early diagnostics and prophylaxis of difference
diseases, human treaction on allergens, hazards effects of some environmental
factors (plant poisons, drug, physicalagents, etc).These demand development
new prognostic methods for evaluation potential dangerous for population health,
including developmental health. In this publication we demonstrate the complex
express methods to estimate the human blood cyto-, geno- and embryotoxic factors
have been worked out. The complex approach consists of the simultaneous usage
of three models: mice preimplantation embryos C57Bl/CBA (from cleavage stage
up to blastocysts formation, 1-5 days of development); rat postimplantation
embryos (head fold stage – 27-30 pairs of somites, 9,5-11,5 days of development)
and culture of human peripheral blood lymphocyte. Mice preimplantation embryos
are simultaneously cytological and embryological test-model being both few-cell
selfdeterminated system and integrated organism. Basing on the model it is possible
to estimate both cytotoxic and embryotoxic effects after pathogenic influence.
Rat postimplantation embryos are the most sensitive model to the pathogenic
influence. The early laboratory animal embryos ability to in vitro development
in human blood sera brought to the working out of cyto-, geno- and embryotoxic
factors estimation methods. The presence of patogens leads to inhibition of
embryo development, cyto- and genotoxic (mutagenic) effects. Embryotoxicity,
embryolethality, teratogenesis (dismorphogenesis), dynamic disorders, cytotoxic
and genotoxic effects are the main criteria for the estimation of distortions
embryo development and lymphocyte culture after pathogenic influence.
At first were worked out conditions for the optimal development of pre-and
postimplantation embryos in sera from blood donors, as well as methods to identify
potential genotoxic factors by using culture human peripheral blood lymphocyte
and methods for detecting frequency of sister chromatid exchanges (SCE) and
micronuclei. To evaluate the cytotoxicity used the cytokinesis block-micronucleus
assay using lymphocyte culture of human blood. A significant advantage
of a comprehensive assessment of embryo-, cyto-and genotoxic factors is the
use of the same blood sample in the different tests. Secondly stage of investigation
carried out testing a comprehensive system for detection and prediction embryopathogenic
risks associated with childbirth in ecologically disadvantaged regions with
hemolytic disease of newborns, as well as factors arising in the humans blood
after acute poisoning (including suicide attempts). The results of the testing
indicate the possibility of identifying and comprehensive assessment of toxic
factors in the blood of people in order to predict risk of pathogenic effects
for human embryo and its genetic apparatus. Experience accumulated material
presented in the form of guidelines on the identification and assessment
of cyto-, geno-, embryotoxic factors in human blood. In perspective test system
will be supplemented by the fourth model: murine embryonic stem cells that will
provide earlier prediction embryopatological changes by identifying the expression
of genes controlling the basic embryonic morphogenetic processes. There will
also be added to the battery assessing mutagenic effects using comet-assay and
other modern molecular genetics techniques.