p xiii.54 - p xiii.54 genetic toxicology studies comparing cigarettes which burn or primarily heat...

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SI06 S·Xll1: Identification and evaluation of environmental mutagens, ecogenotoxicology Ip XIII.541 Genetic toxicology studies comparlna claareltes which burn or primarily heal tobacco David Doolittle, Buddy Brown, Jerry Avalos, David Bombick, Carr Smith, Susan McKarns, Betsy Reed-Bombick. E1Wironmental and Molecular Toxi- cology, R. J. Reynolds Tobacco Co. Winston-Salem, North Carolina The genotoxic potential of smoke from Eclipse, a cigarette that primarily heats rather than bums tobacco, was compared with Kentucky reference IR4F cigarettes, representative of low-tar cigarettes currently sold in the United States. Mainstream smoke condensate from Eclipse cigarettes was negative in the Ames bacterial mutagenicity assays, sister chromatid ex- change (SCE) assays and chromosome aberration assays at concentrations where smoke condensate from I R4F reference cigarettes induced a concen- tration dependent positive response in all assays. Studies on whole main- stream smoke using an in ouro exposure system demonstmted that smoke from the Eclipse cigarette was significantly less active in the SCE assays compared to smoke from an equal number of IR4F reference cigarettes. DNA adducts were evaluated in the lungs and hearts of laboratory mice exposed to whole smoke by the inhalation route as well as the dermal route using smoke condensates. DNA adduets, as measured by the P-32 post-labeling assay, were substantially reduced when animals were exposed to smoke or smoke condensate from Eclipse cigarettes compared to the smoke or smoke condensate from the IR4F reference cigarette. When smokers switched to the Eclipse cigarette, their urine mutagenicity decreased by approximately 75% compared to when smoking their usual brand, Keyword(s): cigarette smoke; tobacco Ip XIII.561 Atmospheric air enntamlnatlon and demographic pro- cessln the cities of Ukraine Alexei Dougan, Olga Timchenko, Elena Touros. USCH, Popudrenka; SO. Kiev-94. Ukraine Experimental data of the invesnganon of atmospheric air chemical content of 18 Ukrainian cities and medical-demographic situation in these cities are presented. 11 has been shown that the most contaminanated cities (on total emission and on emission volume in the atmosphere per capita) are the Cities with mainly developed metallurgical industry: Krivoy Rog, Mariupol. Makeyevka, Zaporoghye, Donetsk. The total emission and emission per capita for them was 1392; 860; 436; 414; 321 thousand tons and 1.99; 1.62; 1.47; 1.0 respectively. An atmosphenc air of the cities with mainly devel- oped chemical industry (Lisichansk, Severodonetsk, Gorlovka, Cherkassy, Kremenchug) was also contammated. An emission per capita in these cities was also rather high. Investigation of the chemical content of the atmospheric air of the mentioned cities (PAH, hard metals, low molecular hydrocarbons of aromatic row) has exposed an exceeding of the established regulation 2-9.1 folds. It has been proved by biotest data in the microorganisms. It is shown, that the total emission of hazardous substances is higher the total air mutagenecity is higher and therefore the risk of unfavourable effect revealing on the health is higher. Observation's data for the life expectancy of the population of the cities mentioned above, and analysis of medical-ecological situation in these cities in the SD-th and first part of the 90-th have led to general conclusion that population of ecologically contaminated industrial cities with mainly development of chemical industry, especially with metallurgical industry are characterised by more nonrational regime of mortality, by lower expecting life duration and unfavourable tendencies of the dynamic of these indices of population viability. Thus contamination of atmospheric air by hazardous substances leads not only to the increasing risk of the frequency ofheredilary pathology but to negative medical-dernographical consequences. Ip XIII.551 Multlvltamlne prophylaxis versus exposure to carcino- genic polycyclic aromatic hydrocarbons (PAUs) Keyword(s): contamination of atmospheric air; mutagenecity Lubomir Dobias', Jaromira Kusova', Jaroslava Havrankova', Jaroslav Sipula z, Alena K1oudova I, Jana Homova z. / Regional Institute of Hygiene, 728 92 Ostraua; Czech Republic, 2 L. Merckle GmbH, Bmo; Wien, Czech Republic The overall response of human organisms to PAHs exposure is a sum of discrete factors, above all: PAHs load rate, biotmnsformation and individual characteristics of susceptibility. Particularly vitamins play the positive role in a field of antimutagenic action after PAHs exposure. The carcinogenic PAHs were found in concentrations from 8.9 nglm3 to 162.3 uglm3 (benzolalpyrene: 1.6 nglm3 - 37.7 uglm3) in workplaces. The biomarkers for PAHs exposure evaluation: cytogenetic analysis, mutagenicity in urine, selected factors of humoral and cellular immunity. Analyzed group and multivitamine prophylaxis: A group of 50 coke oven workers - subgroup A: (25 persons) treated with PREGNAVIT (L. Merckle GmbH); - subgroup B: (25 controls), PLACEBO application. PREGNAVIT or PLACEBO were ad- ministered for 7 months. General Conluslons: After PREGNAVITtreatment the level of chromosomal aberrations (%AB.C) decreased [from 2.20% to 1.27% (P a 0.01)] and other parameters of cIastogenicity (B/C, distribution of %AB.C levels, frequency of types of chromosomal aberrations) too. The re- sults show the differences (decrease in %AB.C, P = 0.01 I) between vitamin- treated workers and control group (PLACEBO). The influence of vitamin supplementation on different levels of mutagenicity in urine in vitammized and non-vitaminized group is also visible. This study did not show significant relationship between the followed-up humoral and cell imuRlty parameters and the effect of multivitamin prophylaxis. These findings support the use of PREGNAVIT as a prophylactic agent for exposed coke oven workers. (Study was supported by Grant of Czech Ministry of Health No. 1696-3, L. Merckle GmbH, Bma-Wien, CR, Managment of NH Colce Oven Plant and HP Insumnce Agency, Ostrava). Keyword(s): PAHs; Genotoxicity; Antimutagenicity Ip XIII.571 Disinfectants application and Induced mutagenesis In lalmonella typhlmurlum Alexei Dougan. USCH, Popudrenco, 50. Kiev-94. Ukraine The aim of the investigation is a demonstration of generation and removal of mutagenetically active compounds with the help of Ames express-method at the example of mam technological chain of water treatment in Dneprovsky water-main (Kiev). Experimental data testilY that raw water from river Dnieper becomes more mutagenic (approximately 1.5-2.0 folds) at its processing by chlorine. Thus it is clear that just chlorine introduces additional activity in river water. Then it is shown that in summer months mutagenecity both river and chlorinated water is higher than in autumn-winter penod. Therefore, algae reproduction also influences on the mutagenic pool. While water goes through other links of the water treatment chain gradual decrease of mutagenecity by coagulation application, settling and filtration through sandy filters. On Dneprovsky water-main ozone is used at finish purification. It leads to the splash of the mutagenecity of samples taken from the ozonizer. To all appearances it takes place because of generation of volatile low molecular chemical compounds which have a possibility to induce gene mutation. The proof of last statement was a fact that the samples from the pure water reservoir (drinking water falling into the general city's water main) had a mutagenecity typical for Kiev water-main, that is, at the rate of week or ''boundary" mutagenecity with corresponding season variation; "boundary" effects have been revealed in autumn-winter period; weak effects - in summer months. Thus on the basis of the fulfilled experiments we can make a conclusion that the use of chlorine as disinfectant undoubtfully deteriorates a drinlc- ing water quality on the potential mutagenecity and carcinogenic actiVity induces. Water mutagenecity is higher in summer period because of heavy algae development, it also influences on drinking water quality. A search

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SI06 S·Xll1: Identification and evaluation of environmental mutagens, ecogenotoxicology

Ip XIII.541 Genetic toxicology studies comparlna claareltes whichburn or primarily heal tobacco

David Doolittle, Buddy Brown, Jerry Avalos, David Bombick, Carr Smith,Susan McKarns, Betsy Reed-Bombick. E1Wironmental and Molecular Toxi­cology, R. J. Reynolds Tobacco Co. Winston-Salem, North Carolina

The genotoxic potential of smoke from Eclipse, a cigarette that primarilyheats rather than bums tobacco, was compared with Kentucky referenceIR4F cigarettes, representative of low-tar cigarettes currently sold in theUnited States. Mainstream smoke condensate from Eclipse cigarettes wasnegative in the Ames bacterial mutagenicity assays, sister chromatid ex­change (SCE) assays and chromosome aberration assays at concentrationswhere smoke condensate from I R4F reference cigarettes induced a concen­tration dependent positive response in all assays. Studies on whole main­stream smoke using an in ouro exposure system demonstmted that smokefrom the Eclipse cigarette was significantly less active in the SCE assayscompared to smoke from an equal number of IR4F reference cigarettes. DNAadducts were evaluated in the lungs and hearts of laboratory mice exposedto whole smoke by the inhalation route as well as the dermal route usingsmoke condensates. DNA adduets, as measured by the P-32 post-labelingassay, were substantially reduced when animals were exposed to smoke orsmoke condensate from Eclipse cigarettes compared to the smoke or smokecondensate from the IR4F reference cigarette. When smokers switched tothe Eclipse cigarette, their urine mutagenicity decreased by approximately75% compared to when smoking their usual brand,

Keyword(s): cigarette smoke; tobacco

Ip XIII.561 Atmospheric air enntamlnatlon and demographic pro­cessln the cities of Ukraine

Alexei Dougan, Olga Timchenko, Elena Touros. USCH, Popudrenka; SO.Kiev-94. Ukraine

Experimental data of the invesnganon of atmospheric air chemical contentof 18 Ukrainian cities and medical-demographic situation in these cities arepresented. 11 has been shown that the most contaminanated cities (on totalemission and on emission volume in the atmosphere per capita) are theCities with mainly developed metallurgical industry: Krivoy Rog, Mariupol.Makeyevka, Zaporoghye, Donetsk. The total emission and emission percapita for them was 1392; 860; 436; 414; 321 thousand tons and 1.99; 1.62;1.47; 1.0 respectively. An atmosphenc air of the cities with mainly devel­oped chemical industry (Lisichansk, Severodonetsk, Gorlovka, Cherkassy,Kremenchug) was also contammated. An emission per capita in these citieswas also rather high. Investigation of the chemical content ofthe atmosphericair of the mentioned cities (PAH, hard metals, low molecular hydrocarbonsof aromatic row) has exposed an exceeding of the established regulation2-9.1 folds. It has been proved by biotest data in the microorganisms. It isshown, that the total emission of hazardous substances is higher the total airmutagenecity is higher and therefore the risk of unfavourable effect revealingon the health is higher.

Observation's data for the life expectancy of the population of the citiesmentioned above, and analysis ofmedical-ecological situation in these citiesin the SD-th and first part of the 90-th have led to general conclusionthat population of ecologically contaminated industrial cities with mainlydevelopment of chemical industry, especially with metallurgical industry arecharacterised by more nonrational regime of mortality, by lower expectinglife duration and unfavourable tendencies of the dynamic of these indicesof population viability. Thus contamination of atmospheric air by hazardoussubstances leads not only to the increasing risk of the frequency ofheredilarypathology but to negative medical-dernographical consequences.

Ip XIII.551 Multlvltamlne prophylaxis versus exposure to carcino­genic polycyclic aromatic hydrocarbons (PAUs)

Keyword(s): contamination of atmospheric air; mutagenecity

Lubomir Dobias', Jaromira Kusova', Jaroslava Havrankova', JaroslavSipulaz, Alena K1oudovaI, Jana Homovaz. /Regional Institute of Hygiene,728 92 Ostraua; Czech Republic, 2L. Merckle GmbH, Bmo; Wien, CzechRepublic

The overall response of human organisms to PAHs exposure is a sum ofdiscrete factors, above all: PAHs load rate, biotmnsformation and individualcharacteristics of susceptibility. Particularly vitamins play the positive rolein a field of antimutagenic action after PAHs exposure. The carcinogenicPAHs were found in concentrations from 8.9 nglm3 to 162.3 uglm3(benzolalpyrene: 1.6 nglm3 - 37.7 uglm3) in workplaces. The biomarkersfor PAHs exposure evaluation: cytogenetic analysis, mutagenicity in urine,selected factors of humoral and cellular immunity. Analyzed group andmultivitamine prophylaxis: A group of 50 coke oven workers - subgroup A:(25 persons) treated with PREGNAVIT (L. Merckle GmbH); - subgroup B:(25 controls), PLACEBO application. PREGNAVIT or PLACEBO were ad­ministered for 7 months. General Conluslons: After PREGNAVIT treatmentthe level of chromosomal aberrations (%AB.C) decreased [from 2.20% to1.27% (P a 0.01)] and other parameters of cIastogenicity (B/C, distribution of%AB.C levels, frequency of types of chromosomal aberrations) too. The re­sults show the differences (decrease in %AB.C, P = 0.01 I) between vitamin­treated workers and control group (PLACEBO). The influence of vitaminsupplementation on different levels of mutagenicity in urine in vitammizedand non-vitaminized group is also visible. This study did not show significantrelationship between the followed-up humoral and cell imuRlty parametersand the effect of multivitamin prophylaxis. These findings support the useof PREGNAVIT as a prophylactic agent for exposed coke oven workers.(Study was supported by Grant ofCzech Ministry of Health No. 1696-3, L.Merckle GmbH, Bma-Wien, CR, Managment of NH Colce Oven Plant andHP Insumnce Agency, Ostrava).

Keyword(s): PAHs; Genotoxicity; Antimutagenicity

Ip XIII.571 Disinfectants application and Induced mutagenesis Inlalmonella typhlmurlum

Alexei Dougan. USCH, Popudrenco, 50. Kiev-94. Ukraine

The aim of the investigation is a demonstration of generation and removal ofmutagenetically active compounds with the help of Ames express-method atthe example of mam technological chain of water treatment in Dneprovskywater-main (Kiev).

Experimental data testilY that rawwater from river Dnieper becomes moremutagenic (approximately 1.5-2.0 folds) at its processing by chlorine. Thusit is clear that just chlorine introduces additional activity in river water. Thenit is shown that in summer months mutagenecity both river and chlorinatedwater is higher than in autumn-winter penod. Therefore, algae reproductionalso influences on the mutagenic pool. While water goes through other linksof the water treatment chain gradual decrease of mutagenecity by coagulationapplication, settling and filtration through sandy filters.

On Dneprovsky water-main ozone is used at finish purification. It leadsto the splash of the mutagenecity of samples taken from the ozonizer. To allappearances it takes place because of generation of volatile low molecularchemical compounds which have a possibility to induce gene mutation. Theproof of last statement was a fact that the samples from the pure waterreservoir (drinking water falling into the general city's water main) had amutagenecity typical for Kiev water-main, that is, at the rate of week or''boundary" mutagenecity with corresponding season variation; "boundary"effects have been revealed in autumn-winter period; weak effects - in summermonths.

Thus on the basis of the fulfilled experiments we can make a conclusionthat the use of chlorine as disinfectant undoubtfully deteriorates a drinlc­ing water quality on the potential mutagenecity and carcinogenic actiVityinduces. Water mutagenecity is higher in summer period because of heavyalgae development, it also influences on drinking water quality. A search