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Original Articles

Further arguments in favour of direct covalent binding of Ochratoxin A (OTA) after metabolic biotransformation

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Pages 75-87 | Published online: 09 Aug 2006

Figures & data

Figure 1. Tests of purification and postlabeling (A) UV spectrum to test purity of DNA; (B) post-labeling efficiency; (C) nuclease P1 efficiency; (D) exemples of good and bad DNA adduct patterns.

Figure 1. Tests of purification and postlabeling (A) UV spectrum to test purity of DNA; (B) post-labeling efficiency; (C) nuclease P1 efficiency; (D) exemples of good and bad DNA adduct patterns.

Figure 2. Influence of the molarity and pH on migration of DNA adduct. (A) Influence of the molarity on D1 migration of the C8 dG-OTA adduct; (B) separation of AA (aristolochic acid) and OTA (ochratoxin A) as function of molarity and pH of D2 & D3 solvents of migration.

Figure 2. Influence of the molarity and pH on migration of DNA adduct. (A) Influence of the molarity on D1 migration of the C8 dG-OTA adduct; (B) separation of AA (aristolochic acid) and OTA (ochratoxin A) as function of molarity and pH of D2 & D3 solvents of migration.

Figure 3. Comparison of OTA-DNA adduct formed in various animal species and in human tumours. MK, mouse kidney; RK. rat kidney; PK, pig kidney; CK, chicken kidney; HK, Human kidney accidental death; HBT, human bladder tumour; HKT, human kidney tumour.

Figure 3. Comparison of OTA-DNA adduct formed in various animal species and in human tumours. MK, mouse kidney; RK. rat kidney; PK, pig kidney; CK, chicken kidney; HK, Human kidney accidental death; HBT, human bladder tumour; HKT, human kidney tumour.

Figure 4. Dose-dependent OTA-DNA adduct formation: (A) OTA-DNA adduct (No. 1) in kidney of mouse and rat treated by gavages, one dose, Panel A grey = mouse, white = rat; (B) OTA-DNA adduct (No. 1) in monkey kidney cells; (C) Comparison of Total DNA adduct formation in kidney of rat after gavage or feed contamination, Panel grey = 0.2 mg/kg bw white = 1 mg/kg bw; (D) Total DNA adduct in kidney of Dark Agouty rat fed 28 days.

Figure 4. Dose-dependent OTA-DNA adduct formation: (A) OTA-DNA adduct (No. 1) in kidney of mouse and rat treated by gavages, one dose, Panel A grey = mouse, white = rat; (B) OTA-DNA adduct (No. 1) in monkey kidney cells; (C) Comparison of Total DNA adduct formation in kidney of rat after gavage or feed contamination, Panel grey = 0.2 mg/kg bw white = 1 mg/kg bw; (D) Total DNA adduct in kidney of Dark Agouty rat fed 28 days.

Figure 5. Typical DNA modification pattern observed after in vitro incubation of polynucleotides or DNA in presence pig kidney microsomes.

Figure 5. Typical DNA modification pattern observed after in vitro incubation of polynucleotides or DNA in presence pig kidney microsomes.

Figure 6. Correlation between DNA adduct and biotransformation enzyme. (A) DNA + microsome without OTA; (B) DNA + OTA without microsome; HHK, human healthy kidney microsome; HPTK, human peri-tumoral kidney microsome; HTK, human tumoral kidney microsme; MK, kidney from mouse pre-treated with vitamin A.

Figure 6. Correlation between DNA adduct and biotransformation enzyme. (A) DNA + microsome without OTA; (B) DNA + OTA without microsome; HHK, human healthy kidney microsome; HPTK, human peri-tumoral kidney microsome; HTK, human tumoral kidney microsme; MK, kidney from mouse pre-treated with vitamin A.

Figure 7. Differences in OTA biotransformation in OK cells treated by several modulators [A] Example of separation of OTA derivatives —— OTA alone —— after treatment with acivicin; [B] Comparison of metabolites formed after pretreatment with

OTA alone
+ MESNA
+ NAC
+ BSO
+ Acivicin.

Figure 7. Differences in OTA biotransformation in OK cells treated by several modulators [A] Example of separation of OTA derivatives —— OTA alone —— after treatment with acivicin; [B] Comparison of metabolites formed after pretreatment with Display full size OTA alone Display full size + MESNA Display full size + NAC Display full size + BSO Display full size + Acivicin.

Figure 8. Mass spectrum of a dechlorinated derivative of OTA.

Figure 8. Mass spectrum of a dechlorinated derivative of OTA.

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