Formation of ochratoxin A metabolites and DNA-adducts in monkey kidney cells.
Monkey kidney cells (named Vero cells) were incubated with increasing doses of ochratoxin A (10-100 microM). The inhibiting concentration 50% (IC50) on protein synthesis was about 14 microM in the presence of 5% fetal calf serum and 37 microM in the presence of 10% fetal calf serum. Some metabolites of ochratoxin A, including the chlorinated dihydroisocoumarin moiety of OTA (OT alpha), 4-[S]-hydroxy-OTA and 4-[R]-hydroxy-OTA were detected by HPLC in the mixture of cell homogenate after a 24 h incubation with 10 and 25 microM of OTA. Using the 32P-postlabelling method, several DNA-adducts, similar to those formed in mouse kidney after OTA treatment, were detected in monkey kidney cells. Thus, Vero cells are suitable for genotoxic and cytotoxic studies in relation to the metabolism of nephrotoxic xenobiotics such as OTA.
Grosse
Y
Y
Ecole Nationale Supérieure Agronomique, Toulouse, France.
Baudrimont
I
I
Castegnaro
M
M
Betbeder
A M
AM
Creppy
E E
EE
Dirheimer
G
G
Pfohl-Leszkowicz
A
A
D000818:Animals; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity*; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D018736:DNA Adducts / Q000096:biosynthesis*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D009793:Ochratoxins / Q000378:metabolism* / Q000633:toxicity*; D014176:Protein Biosynthesis; D014316:Tritium; D014709:Vero Cells
D002273:Carcinogens; D018736:DNA Adducts; D009793:Ochratoxins; D014316:Tritium; C025589:ochratoxin A; D004247:DNA; D007930:Leucine