SVIBOR - Project code: 1-08-146

MINISTRY OF SCIENCE AND TECHNOLOGY

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Project code: 1-08-146


GENOTOXIC RISK ASSESSMENT IN THE AQUATIC ENVIRONMENT BY MOLECULAR BIOMARKERS


Main researcher: KURELEC, BRANKO (24811)


Assistants
Type of research: applied
Duration from: 01/01/91. to 12/31/95.
Papers on project (total): 0
Institution name: Institut "Ruđer Bošković", Zagreb (98)
Department/Institute: Center for Marine Research Zagreb, Division Zagreb
Address: Bijenička cesta 54
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (01) 276-483
Fax: 385 (01) 420-437
Summary: All investigated water organisms possess multixenobiotic resistance mechanism (MXR). They possess verapamil sensitive potential for binding xenobiotics like acetylaminofluorene (AAF) or vincristine; Western blotting and immunohistological methods detected P-170-like protein; accumulation of xenobiotics in the organisms was enhanced in the presence of MXR inhibitors, the chemosenzitizers, verapamil or staurosporine, and the induction of adducts and single stranded DNA brakes was enhanced in fish, sponges and mussels after exposure to aminoanthracene or AAF. MXR chemosenzitizers were found also in the samples from the environment. MXR is inducible and can be used as a biomarker. Carp treated i.p. with BaP induce BaP-related DNA adduct, and when exposed to Diesel-2 oil, a Diesel-2 characteristic DNA adducts. The indigenous DNA adducts found in many aquatic organisms coinceded with their reproductive phase and are endogenous in their nature. The correlation of bile fluorescence with the induction of liver MFO activities offers a cheap tool for monitoring and assessment studies. Analysis of the chlorinated hydrocarbons in sediments and bivalves from eastern Adriatic coastal waters during long-term period shows that the trend of mass fractions of DDT and its metabolites DDE and DDD is more similar to an exponential function than to a linear one. Extracts from sediments collected in the area of Šibenik, contain xenobiotics that induce BaPMO activity but are not mutagenic.

Keywords: resistance mechanism, glycoprotein P-170, bile fluoroscence, Diesel-2 oil, verapamil, DNA adducts, 32 P-postlabeling, mussel, fish, sponge, PAH, sea sediments, coastal pollution, Adriatic sea, DDTs, PCBs, long- term trends, halogenated hydrocarbons.

Research goals: Many aquatic organisms resistant to pollution seem to be simultaneously resistant to multiple toxic xenobiotics, since water pollution is typically caused by a mixture of chemicals. The molecular mechanism of this "multixenobiotic resistance" (MXR) is similar to the mechanism of multidrug resistance (MDR) found in tumor resistant cell-lines: it involves a transmembrane 170,000 kDa glycoprotein (P170) which binds a xenobiotic and facilitates its efflux by an energy-dependent process and hence the decrease in xenobiotic accumulation and xenobiotic resistance. There are compounds that inhibit or block the function of MDR and reverse resistance, like verapamil, a competitive inhibitor of P170. Many toxic and untoxic lipophilic agents, natural or man-made, may also be recognized and processed by this molecular mechanism, and, at high concentrations, they might saturate the system and thereby reverse MXR. In addition to such competitive inhibitors, there are agents that may modulate the regulation of the MXR mechanisms, like modulators of protein kinase C, or modulators of expression of MXR RNA. Since MXR mechanism represents a general biological defense mechanism for protection of organism from natural endogenous and environmental toxins, its inhibition by such "chemosensitizers" may cause adverse effects. Our aim attempts to recognize the presence of such compounds in aquatic environmental samples, to establish their importance for xenobiotic exposure assessment, and to put into perspective the realistic significance of MXR mechanism for the study of pollution effects, environmental monitoring of organisms and risk assessment needed in regulatory policy.

COOPERATION - PROJECTS


  1. Name of project: PN 868, US-EPA Analysis of DNA adducts and other biomarkers as a possible tool for genotoxic risk assessment in the aquatic environment
    Name of institution: Environmental Protection Agency
    City: Washington, SAD

  2. Name of project: ICP/CEH 039-YUG Biomarkers for genotoxic risk assessment in the marine environment
    Name of institution: United Nations Environmental Programme/World Health
    City: Atena, GR

  3. Name of project: ME 5101-89-02 The environmental implications of the multixenobiotic-resistance mechanism expressed in marine invertebrates
    Name of institution: Food and Agriculture Organisation/Mediterranean Action Plan
    City: Atena, GR

  4. Name of project: Biostress
    Name of institution: International Buero GKKS
    City: Geesthacht, Njemačka

  5. Name of project: 302-K4-CRO-7825 Quantification of multixenobiotic resistance inhibitors in aquatic environment
    Name of institution: International Atomic Energy Agency
    City: Beč, Austrija

  6. Name of project: No-obligation cooperation on research on DNA adducts
    Name of institution: Graduate Center for Toxicology, University of Lexington
    City: Lexington, USA

  7. Name of project: No-obligation cooperation on research on multidrug resistance (MDR)
    Name of institution: National Institute of Haematology, blood transfusion and immunology
    City: Budimpesta, Madjarska

  8. Name of project: Studija ugrozenosti voda i pristup optimalnom rjesavanju ratnih otpada na krskom podrucju
    Name of institution: JVP Hrvatska vodoprivreda, Yagreb
    City: 10000 - Zagreb, Croatia

COOPERATION - INSTITUTIONS


  1. Name of institution: Mediterranean Action Plan
    Type of institution: State administration
    City: Atena, GR

  2. Name of institution: Institut za medicinska istraživanja i medicinu rada
    Type of institution: University/Faculty
    City: 10000 - Zagreb, Croatia

  3. Name of institution: Glavni stožer saniteta Republike Hrvatske
    Type of institution: Institution whose primary activities ar
    City: 10000 - Zagreb, Croatia

  4. Name of institution: JVP Hrvatska vodoprivreda
    Type of institution: Institution whose primary activities ar
    City: 10000 - Zagreb, Croatia
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