Cytogenetic effects of quinoxaline-1,4-dioxide-type growth-promoting agents. I. Micronucleus test in rats.

The cytogenetic activities of 3 growth-promoting agents carbadox, olaquindox and cyadox were examined by the micronucleus test. These chemicals were administered i.p. to male Wistar rats 30 and 6 h before they were killed. Single-dose levels were 5, 10, 15, 30, 60, 90, 120 and 240 mg/kg for carbadox; 30, 60, 90, 120 and 240 mg/kg for olaquindox; and for cyadox 30, 60, 120 and 240 mg/kg. Over the entire dose range tested, carbadox induced a statistically significant increase in the number of micronucleated polychromatic erythrocytes in the rat bone marrow, whereas similar activity of olaquindox started at a dose of 2 X 60 mg/kg. The effect of cyadox was very low even at the highest dosage tested. Further testing of the genotoxicity of this class of chemicals is required. The genetic activity of the solvent used (dimethyl sulfoxide) is briefly discussed.

Monitoring of effects of cis-diamminedichloroplatinum II. Part I. Cytogenetic analysis in vitro.

The cytogenetic effects of cytostatic drug Platidiam Lachema (cis-diamminedichloroplatinum (II) complex, cis-DDP) have been studied employing short-term in vitro cultivation of human peripheral lymphocytes. Three hours following the administration of cis-DDP at a concentration of 12.5 microM (that is a concentration approximately 10 times lower than that applied clinically at a single dose), chromosome aberrations (predominantly breaks, in 73% those of the chromatid type) were seen at an increased rate. They reached their maximum after 24 h of treatment. A time dependence has been revealed: with decreasing mitotic activity and prolonged time of cis-DDP treatment (3, 6, 18, 24, 48, 72 h, respectively) the number of cells with aberrant chromosomes increased, this elevation being statistically significant from 18 h on.

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.

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.

Monitoring of effects of cis-diamminedichloroplatinum II (Platidiam). Part II. Tests for mutagenic activity in the indicator system of Salmonella typhimurium his- strains (Ames test).

The mutagenic activity of the cytostatic drug Platidiam (cis-diamminedichloroplatinum II complex, cis-DDP) produced in Czechoslovakia was tested. In the used Ames test, as an indicator system, Salmonella typhimurium his- strains were employed. The tests for mutagenicity were performed in vitro using assays both without metabolic activation and therewith, as well as with metabolic activation under in vivo conditions. The analyses revealed a mutagenic effect of the cis-DDP complex in Platidiam in all of the followed tests. These effects were direct, no metabolic activation was observed. Furthermore, the mutagenic activity of the drug was influenced by the duration of interaction between Platidiam and the mammalian organism, which was apparently due to the pharmacokinetic properties of the active substance.

Cinemicrographic analysis of the cellular changes of the stabilized cell line HeLa provoked by l-aminoadamantane.

The effect of antiviral compound l-aminoadamantane on HeLa cell culture has been studied. Morphological changes were observed at the concentration 300 and 500 mug/ml. The concentration of 150 mug/ml exerted a delay in the process of cell adhesion and dilatation (spreading).

Environmental health.

A short history of the close connections between human health an ambient environment (environmental health) in the global and national (Czech Republic) sense is presented. Concrete tasks and prospects for the near future are mentioned, including the human ecology education programme.

Long-term monitoring of the immune reactivity of stainless steel welders.

The immune reactivity of stainless steel welders (n = 22-53) was evaluated in a three year's study. The results (phagocytic activity, cellular and humoral immunity) were statistically compared with those in control group of non-exposed persons from the same plant (n = 14-23) and with long-term laboratory reference values (LRV) (n = 14-311). In welders several changes were found when compared to the LRV: in humoral response there were higher prealbumin, lysozyme, circulating immune complexes and lower IgG. In phagocytic tests there were lower ingestion, bactericidal activity and higher metabolic activity of peripheral mononuclear leucocytes. In cellular immunity the marked lymphocytosis, higher counts of T-lymphocytes, CD4+ and CD8+ lymphocytes were noticed. After lowering the concentrations of metals in the working area there were trends to normal values in some parameters [relative numbers of T-lymphocytes, relative number of CD4+ lymphocytes, phagocytic activity, metabolic activity of leucocytes (INT index), IgA, complement C3, transferrin]. The extent and the length of the exposure to welding fumes, smoking and changed conditions at working place were followed as well.

To the history and evolution of hygiene and preventive medicine at the Faculty of Medicine of Charles University in Hradec Králové.

In a dynamic sequence there has been presented longer than 50 years lasting history of the branch "Hygiene" (after the year 1989 joined with "Preventive Medicine") in the University Department of the same name of the Medical Faculty of Charles' University in Hradec Králové since the year 1945 till today. The modern primary preventive medical field "Hygiene and Preventive Medicine" today not only covers the medical studies but, at the same time, represents a complex integrating general ecological approach to solving most of problems of public health, environmental one included. Ensuring the global good conditions for man during his permanently sustainable healthy living and development being the ultimate goal.

[Evaluation of carcinogenic risk at the international (International Agency for Research on Cancer--World Health Organization) and the Czechoslovak level. A basis for consideration prior to amending Guideline no. 64/1984 on hygienic principles in working with chemical carcinogens]. / Posuzování karcinogenního rizika na mezinárodní (IARC-WHO) a ceskoslovenské úrovni. Nekolik podkladu k zamyslení pred novelizací Smernice c. 64/1984 o hygienických zásadách pro práce s chemickými karcinogeny.

The aim of the International Agency for Research on Cancer (IARC) attached to WHO is to facilitate world-wide cooperation in cancer research in the fields of science, methodology, information service, organization or even legislation. For this purpose the IARC publishes specialized monographs containing critical evaluation of risk materials, their mixtures as well as assessment of working procedures involving the risk of carcinogenesis. Within the IARC scope, so far 700 agents have been submitted for comprehensive investigation from the genotoxic aspect, and 628 out of these yielded valid results; 50 agents listed in Group 1 of demonstrable carcinogens, Group 2 contained 196 agents suspect of various degrees of carcinogenicity (subgroups 2A and 2B). The author compares the internationally accepted list of high-risk agents with the present Czechoslovak list--Guidelines No. 64/1984 containing 15 demonstrable carcinogenic agents and 17 potential carcinogenic agents, and he recommends that the prospective Amendment to the Guidelines No. 64/1984 should respond more keenly to the IARC conclusions and recommendations.

[The quality of demographic development in Czechoslovakia from the European viewpoint]. / Kvalita populacního vývoje v CSFR z evropského pohledu.

Forty years of a totalitarian regime imply economic, cultural and moral devastation. Statistical analyses reveal, however, also demographic devastation in particular in the sphere of health and social aspects. This means that the basic indicators of the quality of demographic development in Czechoslovakia during the last 25 years are remarkably close to the indicators of the former socialist system and that they deteriorate and lag behind when compared with other countries, in particular developed industrial countries. This trend can be also called "balkanization" because Czechoslovakia which belonged before the war among the eight most highly developed industrial countries dropped at the end of the eighties to the level of demographic indicators of Bulgaria, Jugoslavia, Hungary, Roumania etc. In the submitted investigation the authors demonstrate these facts based on the analysis of selected coefficients of quality of the demographic development such as infant mortality, specific mortality of the male and female population aged 55-59 years and the mean life expectancy of men and women at birth, on the background of the general European demographic situation. For analyses only the latest data published by UNO were used.

[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.

[Infant mortality throughout the world and its prognosis to the year 2025]. / Kojenecká úmrtnost ve svete a její prognóza do roku 2025.

PIP: A review of infant mortality trends in Europe from 1950 to 1985 is presented using data from published U.N. sources and with emphasis on trends in Eastern Europe and Czechoslovakia. Consideration is also given to future trends up to 2025, and the differences between the U.N. and Czechoslovak projections are compared. (SUMMARY IN ENG AND RUS)^ieng

[Projection of the population in Czechoslovakia to the year 2010 and the economic consequences]. / Projekce obyvatelstva CSSR do roku 2010 a ekonomické dusledky.

PIP: A projection of the population of Czechoslovakia up to the year 2010 is presented, with emphasis on changes in the age distribution and in the available labor force.^ieng

[New projections for the world population to the year 2025]. / Nové projekce obyvatelstva sveta do roku 2025.

PIP: The 1982 and 1984 population projection program of the United Nations containing estimations for the world's population for 2000-2025 had 3 variations: the median projection figure for 2000 was 6.122 billion and for 2025 8.025 billion. The respective figures of the high estimate were 6.340 and 9.088 billion, and the low estimate envisioned 5.927 and 7.358 billion people, respectively. THe corresponding rate of growth is expected to slow down from 1.67% during 1980-1985 to 1.38% during 2000- 2005, and to drop to 0.96% during 2020-2025. The rate of growth of the global population is to decrease from 37.6% during 1980-2000 to 27.4% during 2000-2020. The difference of the projections of 1982 and 1984 is only 29 million people (8.177 and 8.206, respectively). During the period 2000-2020 the population of Africa is expected to grow to make up 11.5% of the world's population, Europe would make up 10.20% and Asia 58.2%. By 2025 the respective figures would be 19.7%, 6.4%, and 55.3%. The rate of growth of 4 European regions would vary during 1980-2000 and 2000-2025: in Eastern Europe 10% and 7.3%, respectively, in Western Europe 2.0% and 0.0%, in Southern Europe 9.2% and 3.9%, and in Northern Europe 1.6% and -2.8%, respectively. The negative growth figures of the German Democratic Republic were revised from 1982 estimates to show a 2.5% and 2.4% increase during the respective periods. The slight increases (1.8% and 0.2%) projected for Hungary were reversed to zero or negative growth (0.0% and -0.8%). During these periods the growth figures for Czechoslovakia would be 8.3% and 8.0%, for Poland 14.7% and 9.2%, for Romania 15.2% and 11.4%, and for Bulgaria 7.6% and 4.6%, respectively. Life expectancy for the periods 1985-1990 and 2010-2025 is estimated at 61.1 and 70.5 years for the world, and 74.0 and 77.2 years for Europe.^ieng

[Biological monitoring of chemical exposure]. / Biologické monitorování chemické expozice.

In this paper we described the biological monitoring as a capable exposure assessment tool that has provided important information used in public health decisions. Biological monitoring is based on determination of biological markers of exposure which are presented as the quantity of a chemical substance or its metabolites or as the deviation of biological parameters (enzyme activity etc.) induced by this substance in exposed humans. The greatest advantage of biological monitoring is the fact that the biological marker of exposure is more directly related to the adverse effects than any environment measurement. Another advantage of biological monitoring is based on the reality that the nonoccupational background exposure (leisure activity, residency, dietary habits, smoking, etc.) may also be expressed in the biological level. Biological parameters can be unfortunately affected by various factors that influence the fate of xenobiotic in vivo. The "BEL" (BTV-biological tolerance value for occupational exposures) is defined as the maximum permissible quantity of a chemical substance or its metabolites or the maximum permissible deviation from the norm of biological parameters during or after exposure. It should be subject to regular revision in the light of new scientific data.

[Chemical load in the population and its evaluation]. / Chemická zátez populace a její hodnocení.

Human health is determined by the interplay between heredity and the environment. Air, water, food and soil contain chemical, physical and biological agents some of which are known to be harmful to health. Chemical substances that pose the risk to human health and safety and to the environment are subject to governmental regulation. The regulatory decision-making process and regulatory actions are based on two distinct elements: risk assessment and risk management. Air pollution (outdoor, indoor) is a world problem afflicting densely populated urban centers and heavily industrialised areas. Industrialization and the widespread use of chemicals coupled with modern intensive agricultural practices have raised a global concern about the contamination of soil and water. Three categories of environmental chemical contaminants generally occur in food--natural and synthetic organic compounds and traces of toxic metals. Human health protection against chemical exposure can be realised in three ways. Environmental monitoring assesses exposure to a chemical agent by measuring its concentration in the environment (i.e., air, soil, food, water). Biological monitoring assesses internal exposure to a chemical agent by measuring the chemical, its metabolites or nonadverse biological response in body fluids, tissues, expired air or excreta. Health surveillance entails the periodic medical examinations of exposed humans with the purpose of protecting health and preventing disease.

[New findings in monitoring health status of welders and grinders of stainless steel]. / Novejsí zkusenosti se sledováním zdravotního stavu svárecu a brusicu nerezových ocelí.

During the occupational preventive care check up we investigated a group of 20 stainless steel welders and grinders in the factory producing technology for chemical industry. Results have been compared with 21 healthy persons--blood donors. In the group exposed there have not been discovered any marked deviations in either their health status, or in the CBC and biochemical screening results, though there had been found substantially increased chromium and nickel concentrations, mainly in grinders. Also the levels of polycyclic aromatic hydrocarbons were in some cases even higher than on the busy city crossing. The chromosome aberrations investigations proved to be very sensitive and confirmed that employees of the followed up factory are exposed to an increased genotoxic risk.

[Polycyclic aromatic hydrocarbons. II. Toxic effects]. / Polycyklické aromatické uhlovodíky. II. Toxické úcinky.

Polycyclic aromatic hydrocarbons (PAH) represent dangerous environmental pollutants. Many of them have toxic and carcinogenic potential. Presented work summarizes most of available data on the absorption, metabolism and elimination of PAH. The second part of article contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. In the third part of article, the populations with higher susceptibility to exposure to PAH are described and the influences of chemical interaction of PAH to biological effects are mentioned.

[Polycyclic aromatic hydrocarbons. Biological indicators of exposure and possibilities of prevention]. / Polycyklické aromatické uhlovodíky. III. Biologické ukazatele expozice a moznosti prevence.

Polycyclic aromatic hydrocarbons (PAH) represent an extensive group of ubiquitous environmental pollutants disposing of a considerable toxic and carcinogenic potential. According to the IARC data (International Agency for Research on Cancer), PAH represent the largest group of chemical carcinogens produced during combustion, pyrolysis and pyrosynthesis of organic matter. PAH can be identified in atmosphere, water, soil, food and other materials which are in daily contact which the general population. Presented work summarizes most of available data on the biological markers used to identify or quantify the exposure to PAH and on the biological markers used to characterize the effects caused by PAH. The digest of possibilities of reduction toxic effects of PAH concludes the work.