[Molecular and cellular aspects of dioxin toxicity].

BACKGROUND: Using methods of molecular toxicology to study dioxin intoxication consequences the contribution was accessed of pathologic alterations induced and manifested by specific biomarkers and ecogenetic effects among Vietnamese population living on contaminated territories. The causes of variability in individual sensitivity to toxic activity were also evaluated. MATERIALS AND METHODS: Individual biomedical indices were compared between those living in contaminated with dioxins (n = 8142) and control (n = 4421) regions. Dioxin concentrations were measured by high resolution chromato-mass spectrometry (84 samples). The characteristics of cytochrome P-450 system state (94 persons) and cytogenetic parameters (368 persons, 331 450 cells) reflected the molecular and genetic effects. Variable sensitivity to dioxins was demonstrated by associations of genetic polymorphism (CYP1A1, GSTM1, GSTT1, n = 195) and congenital morphogenetic variants among children (n = 1734). RESULTS: Numerous consequences were demonstrated among the exposed individuals: noticeable absobtion of dioxins from environmental objects; direct effects of P-450 system's induction; systemic alterations in nucleus and genetic stability; changes in cellular generation's rate. The associations were revealed of genetic polymorphism in xenobiotic biotransformation/detoxification system and the peculiarities of development and morphogenesis among exposed children. CONCLUSION: Characteristics of population chronicle intoxication with dioxins permitted to describe its numerous preclinical and clinical manifestations, to show the key elements in pathogenesis of revealed alterations. Future investigations are to create the groundwork for developing a method for prevention of dioxin pathology induction and realization based on revealing preclinical signs and effects of intoxication.

[The congenital morphogenetic variants and genetic polymorphism of the system of xenobiotic detoxication in children living in dioxin-contaminated regions of South Vietnam].

The presence of dioxins and dioxin-containing ecotoxicants (DCE) in human environment leads to multi-level homeostasis disbalance and, eventually, dioxin pathology (DP) develops. This was demonstrated for the adult population of South Vietnam (1), who had suffered from the use of military chlorphenoxiherbicides to which dioxins had been added. The subjects of this study were children who belonged to the second generation of the inhabitants of DCE-polluted South Vietnam areas. In this sample, the frequency of malformations depending on two factors, genes GSTMI, GSTT1, CYP1A1 genotypes, and DCE exposure, were estimated. The study demonstrates that an increased level of congenital morphogenetic variants per one child is associated with the presence of DCE in the environment, as well as the fact that this parameter is influenced by genotypes of xenobiotic detoxication genes.

[Long-term ecological and genetic consequences of use of dioxin-containing environmental agents]. / Otdalennye ékologo-geneticheskie posledstviia vozdeistviia doksinosoderzhashchimi ékotoksinami.

The long-term consequences of the use of dioxine-containing ecotoxic agents in the USA in 1961-1972 are ecologically and genetically characterized. There were increases in the incidence of pathological reproductive events in the contaminated region. It is concluded that there will be higher probability of abnormalities in the families of individuals born at war or just thereof. An association of impaired reproduction with functional disorders and women's poorer health, with higher incidence of somatic and gynecological diseases (chronic ones in particular) is shown. Cytogenetic changes in the lymphocytes were found in individuals from exposure risk groups. The contribution of chromosomal alterations observed in the contaminated area to immunodeficiency is appreciated. The systemic pattern of the action of biologically active properties of dioxine was demonstrated from the morphofunctional changes of different cell types. Cluster analysis revealed associations of cytogenetic parameters with the integrated index of health status in individuals from different contaminated areas. The ecological and genetic consequences may be regarded as part of homeostatic changes at many levels, as suggested by a correlation between the genetic instability and the changes occurring in other tissues, organs, and systems.

[Detection of micronuclei in desquamating cells of the human oral mucosa in the territory of South Vietnam]. / Registratsiia mikroiader v slushchivaiushchikhsia kletkakh slizistoi rotovoi polosti cheloveka na territorii Iuzhnogo V'etnama.

The possibility of applying the micronucleus test to estimate changes in chromatin structures of somatic cells of South Vietnam inhabitants exposed to with phytotoxic substances (Agent Orange) in the 1960s was investigated. Remote medical and biological consequences of the action of dioxin-containing phenoxyherbicides on man were studied. In inhabitants of Bin Mi Village (Shongbe Province), which had been intensely bombed with Agent Orange, the epithelium of the oral cavity showed a considerable increase in the occurrence of cells with damaged chromatin structures (P < 0.01).

[The enzymes of mono-oxygenase oxidation in the lymphocytes and liver of persons subjected to chlorophenoxy herbicide exposure]. / Issledovanie fermentov monooksigenaznogo okisleniia v limfotsitakh i pecheni liudei, podvergavshikhsia vozdeistviiu khlorfenoksigerbitsidov.

The activity of benzopyrene hydroxylase (cytochrome P-450IA1) was studied in a mitogen-stimulated culture of peripheral blood lymphocytes from residents of the South Vietnam area treated with chlorophenoxy herbicides in the years of American aggression. The population residing in the untreated territory served as the control. The basal and induced benzopyrene hydroxylase activities, as well as the inducibility ratio were determined for each patient using the "lymphocytic test". The content of antipyrine metabolites and their percentage were estimated in the urine of the same patients using the antipyrine test. The computer processing of data allowed to perform primary analysis of the monooxygenase system in lymphocytes by groups in order to reveal correlations between the content of antipyrine metabolites in the urine and the cytochrome P-450IA1 in blood lymphocytes. The effect of residual amount of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) on the human monooxygenase system is discussed.