Induction of DNA single-strand breaks and DNA synthesis inhibition by patulin, ochratoxin A, citrinin, and aflatoxin B1 in cell lines CHO and AWRF.

Four mycotoxins, patulin, ochratoxin A, citrinin, and aflatoxin B1 (AFB1), were compared for their cytotoxicity, DNA synthesis inhibition and DNA damage in CHO and AWRF cells. The concentrations causing a 50% inhibition of colony formation in CHO cells were 0.07, 33, 31, and 10 micrograms/ml, respectively, for patulin, ochratoxin A, citrinin, and AFB1. Values obtained for AWRF cells were 0.011, 6.4, 6.7, and 0.15 micrograms/ml, respectively. Patulin strongly inhibited DNA synthesis in both CHO and AWRF cells, at concentrations over 4 micrograms/ml. Ochratoxin A and citrinin elicited mild inhibition of DNA synthesis (up to 20%) at concentrations greater than 50 micrograms/ml. AFB1 at concentrations over 5 micrograms/ml strongly inhibited DNA synthesis in AWRF cells but stimulated DNA synthesis in CHO cells. In accordance with these findings, AFB1 induced single-strand breaks in the DNA of AWRF cells only. Patulin induced about the same levels of DNA breaks in both types of cells, at concentrations greater than 2 micrograms/ml. Citrinin and ochratoxin A produced DNA breaks in CHO cells, at a very high concentration of 200 micrograms/ml. The number of breaks induced in AWRF cells was not statistically significant. The results suggest that the different effects of AFB1 on CHO and AWRF cells are due to the different ability of these cells to metabolize AFB1 to the ultimate carcinogen AFB1-8,9-oxide by microsomal cytochrome P-450-dependent oxygenases. The effects of the other mycotoxins not requiring the metabolic activation were comparable for both cell types.