| Disease | OCHRATOXIN A (OTA) IA A MYCOTOXIN WHICH HAS BEEN IMPLICATED IN BALKAN ENDEMIC NEPHROPATHY, A DISEASE CHARACTERIZED BY A HIGH INCIDENCE OF URINARY TRACT TUMORS. IT INDUCED DNA SINGLE-STRAND BREAKS AND HAS BEEN SHOWN TO BE CARCINOGENIC IN TWO
RODENT SPECIES. FOR A BETTER UNDERSTANDING OF THE OTA GENOTOXIC EFFECT, OTA-DNA ADDUCT FORMATION AND DISAPPEARANCE HAS BEEN MEASURED USING THE 32P-POST LABELLING METHOD AFTER ORAL ADMINISTRATION OF 2.5 MG/KG OF OTA TO MICE. IN KIDNEY, LIVER AND
SPLEEN, SEVERAL MODIFIED NUCLEOTIDES WERE CLEARLY DETECTED IN DNA, 24H AFTER ADMINISTRATION OF OTA, BUT THEIR LEVEL VARIED SIGNIFICANLTY IN A TISSUE AND TIME DEPENDENT MANNER OVER A 16-DAY PERIOD. TOTAL ADDUCTS REACHED A MAXIMUM AT 48H WHEN 103,
42 AND 2.2 ADDUCTS PER 109 NUCLEOTIDES WERE FOUND RESPECTIVELY IN KIDNEY, LIVER AND SPLEEN, INDICATING THAT KIDNEY IS THE MAIN TARGET OF THE GENOTOXICITY AND LIKELY CARCINOGENICITY OF OTA. THE MAJOR ADDUCT DIFFERED BETWEEN KIDNEY AND LIVER. ALL
ADDUCTS DISAPPEARED IN LIVER AND SPLEEN 5 DAYS AFTER COMPOUND ADMINISTRATION, WHEREAS SOME ADDUCTS PERSISTED FOR AT LEAST 16 DAYS IN THE KIDNEY. SOME ADDUCTS WERE ORGAN SPECIFIC. THE FINDING THAT THE ADDUCTS ARE NOT QUANTITATIVELY AND
QUALITATIVELY THE SAME IN THE THREE ORGANS EXAMINED IS LIKELY DUE TO DIFFERENCES OF METABOLISM IN THESE ORGANS, LEADING TO DIFFERENT ULTIMATE CARCINOGENS AND MAY ALSO RESULT FROM DIFFERENCES IN THE EFFICIENCY OF REPAIR PROCESSES. |