[Genotoxic activity test of sodium fluoride in vitro]. / Testování genotoxické aktivity fluoridu sodného in vitro.

The artificial drinking water fluoridization provided as a mass preventive measure against dental decay poses another substantial problem which is a possibility of genotoxic action. Up to this date, this matter remains still obscur and is discussed with more or less intensity from time to time. The mentioned fact supported authors to study the impact of short-term 24 hrs sodium fluoride (NaF) action in concentration range of 0-500 mg.1(-1) drinking water in the frame of so-called minimal testing set (analysis of chromosomal aberrations in human peripheral lymphocytes, Ames test). For the initial NaF concentration applied, the reference value of 1 mg per 1 liter artificial fluoridization was estimated. The use of Ames test with TA 98 and TA 100 Salmonella typhimurium (+/- S9) strains showed no significant increase in revertants responsible of NaF mutagenic activity in any of applied concentrations (0-1300 mg per 1 Petri dish; = 0-520 mg.l-1 converted to the basic supplementative dose). Cytogenetic analysis of peripheral lymphocytes showed more sensitivity than prototrofic salmonella test. Yet one order higher NaF concentration than its application norm 1 mg.l-1 (i.e. 11 mg.l-1) has induced the occurrence of 3.8% ABB after single addition for 24 hrs to the "healthy" blood cultivated in vitro at short-term. This accounts for a value close to the level of statistically significant difference with regard to the application norm recommended. This level has been even exceeded as for a total count of fragments and exchanged parts. Thus the two orders higher NaF concentration (110.0 mg.l-1) resulted in a strong increase of cells with chromosomal aberrations for all of indicators observed; e.g. 27.5% ABB. Based on literary sources, obtained results and properly experience in practical proceeding artificial fluoridation, the authors concluded that the latter is not adequate to the up-to-date status of knowledge. Besides of economical and technical problems, those scientific are mainly concerned with making doubtful the auto-presumed genotoxic inertness for chronic users of fluoridated drinking water. Author's opinion is that when necessarily provided, the artificial fluoridization of drinking water should be proceeded selectively (in accord with real requirements of an appropriated population group, its age structure and location), temporarily and with intermittent checkout of fluoridization application regimen. To conclude, authors recommend further observation with use of biological model situations in vivo.

[Environmental monitoring and biological monitoring of young people exposed to nonoccupational levels of formaldehyde, toluene and other hydrocarbons]. / Monitorování prostredí a biologické monitorování mladistvých, neprofesionálne exponovaných nízkým koncentracím formaldehydu, toluenu a jiných uhlovodíkû.

During the period of 1983-1985, in two of apprentice schools of P. town the health disorders were investigated in the total of 82 apprentices 15-18 years old from the environment with elevated concentrations of formaldehyde and toluene. The study was contrasted with a control total of 42 apprentices. Cytogenetical examination has been performed, and selected immunological parameters in both blood serum and saliva have been assessed with red and white blood cells counts including differential formula of white blood cells. In addition, the atmospheric toxicity of formaldehyde and vapours of organic solvents (toluene, xylene, varnish naphtha) was measured. A single biological exposure test has been performed for the detection toluene. Statistically significant were differences in occurrence of cell chromosomal aberrations between the group of long term formaldehyde and toluene exposure (averagely 3.53% ABB) and controls (2.21% ABB) as obtained in 1983 and 1984, and so were differences between the long term-to-toluene exposed group (3.30% ABB) and the above mentioned control group as obtained in 1984. No similar results were stated between the long term-to-formaldehyde exposed (3.07% ABB) and control (2.55% ABB) groups in 1985. The main evidence consisted in finding the genotoxical/clastogenic effect of observed agents associated with mainly chromosomal abnormalities of chromatide type. It outflowed from the determination of selected serum proteins (Ig and acute phase proteins) and salivary lysozyme that the group under the combined influence of formaldehyde and toluene showed significantly lower IgG and higher alpha-1-antitrypsin (A1AT). The group at risk of toluene was characteristical in elevated concentrations of alpha-2-macroglobulin (A2M) and A1AT. Most pronounced changes in first year had been revealed through the evaluation of the influence of the duration at risk (significant decrease in IgA and prealbumin, and the increase in A2M and A1AT). The infectious disease as experienced 2 month prior the collection resulted in a significant decrease of IgM, A2M and A1AT in risky groups in individuals with infection in anamnesis. Salivary lysozyme concentration of apprentice environmentally exposed to formaldehyde in the noon showed the decrease, whereas its increase occurred in controls with the difference on 5% significancy level. Blood count assessements showed no significant differences between the investigated values as well as any were assessed between the incidence of health disorders of apprentices and their correspondance to the given group.

[Use of cytochalasin B in the micronucleus test in human peripheral lymphocytes]. / Aplikace cytochalasin B mikronukleus testu v lidských periferních lymfocytech.

The micronucleus test is one of the alternative procedures of cytogenetic analysis. Its modification with the use of cytochalasine B (Calbiochem AG) ensures safely the recording of changes of the genetic apparatus in the first cellular cycle after an attack of a mutagenic agent on human peripheral lymphocytes. The authors elaborated a reproducible modification of the original work of Fenech and Morley--published in this country by Kocisová and Srám--and describe in detail its individual steps. The cytochalasine MN-test which should become part of obligatory standard procedures of Czechoslovak preventive health services (formerly hygiene service) is thus open to confirmation.

[Cytogenetic analysis of the effects of selected 2d generation cytostatics (iproplatin and oxoplatin) on human peripheral lymphocytes in vitro]. / Cytogenetická analýza úcinku vybraných cytostatik II. generace (iproplatina a oxoplatina) na lidské periferní lymfocyty in vitro.

Cytostatic effect of Iproplatinum (CHIP, cis-dichlorotrans-dihydroxy-bis-isopropylaminoplatinic complex) and Oxoplatinum (oxo-Pt, cis-diamin-dichloro-trans-dihydroxyplatinic complex) is studied as influencing genetic structures of in vitro human peripheral lymphocytes. Both mentioned substances are classed as prospective cytostatics with satisfactory effect on various tumors, and both undergo now preclinical tests in our country. They are supposed to cause less undesired side effects in comparison with previous preparation of this range--cisplatinum (cis-DDP; Platidiam). The genotoxicity of both substances is examined using the short-term test (72 hrs.), which means a cultivation of raw human peripheral blood modified according to Macek (1965). To set the testing scheme, five concentrations of substances (0, 5, 12, 60 and 120 mumol.l-1) were selected as well as three time intervals of action of a substance (3, 6 and 24 hrs.) prior the expiration of cultivation time, i.e. before the mitotic cycle stop in c-metaphase. Concentrations were determined estimating cisplatinum's dosage to patients. The concentration value 120 mumol.l-1 responds in theory to a single therapeutic dose administration of Platidiam. However, in praxis this concentration is never achieved in organism (resp. protein-binding effect). In accordance with mice LD50 values, both the Iproplatinum and Oxoplatinum showed experimentally 10 times less toxicity than cis-DDP. Cytogenetic changes were evaluated by microscopy in peripheral lymphocytes (predominantly the occurrence of chromosome abnormalities in metaphase), and mitotic activity was as well identified.

Cytogenetic monitoring of a 24-hour effect of ethylmalonate platinum complex on human peripheral blood lymphocytes.

Analyses of mitotic activities and chromosome aberrations in lymphocytes of human peripheral blood have been utilized to evaluate 24-hour cytotoxic and genetic effect of various concentrations (0, 12, 60, 120, 240, 360 mumol l-1) of ethylmalonate platinum (EM-Pt) in vitro. EM-Pt was found to exert a mutagenic action, to have the character of a clastogenic agent and to affect primarily the G1-phase of the cellular cycle. Its activity may be affected by the concentration of the agent: a direct dependence was observed as regards occurrence of chromosome aberrations and an indirect one with regard to values of mitotic activity and cytotoxicity.

Chromosome aberration and mitotic activity in human peripheral blood lymphocytes following in vitro action of platinum cytostatics cis-DDP and EM-Pt.

Platinum-based preparations, the commercially available Platidiam (Lachema, Brno; cis-diaminodichloroplatinum) and the second generation experimental version--ethylmalonate platinum complex--EM-Pt (Institute of Macromolecular Chemistry, Czechoslovak Academy of Sciences, Prague) were left to act 3, 6 and 24 h on human peripheral blood lymphocytes, cultured in vitro for a short period of time. The utilized concentrations affected cell mitosis, provoking chromosome aberrations. A relationship was found between the effect of the concentration employed and the duration of action of the agent. cis-DDP proved to be a more powerful clastogenic agent than EM-Pt. Under in vitro conditions, neither of the two cytostatics required metabolic activation to trigger its action.