Comparative genotoxic effects of acute vs. fractionated exposure to ochratoxin a and patulin in TP53-deficient and competent cell lines

Abstract

The cytotoxic and genotoxic potentials of ochratoxin-A (OTA) and patulin (PAT) as a result of the 24-hour acute and 10-day chronic approaches. In the 10-day dosing method, the acute doses were fractionated into 10 parts and administered to the cells daily. The TP53 effect on these chemicals were investigated using the lymphoblastoid cell lines TK6 (TP53-compotent) and NH32 (TP53-null). The 24-hour PAT treatment was found to cause greater cytotoxic and genotoxic effects than the 10-day PAT treatment, but this was not true for OTA. The 10-day OTA treatment caused increasing DNA damage frequency when compared to the 24-hour treatment in both cell lines. The 10-day treatment made both mycotoxins less cytotoxic. NH32 presented a significantly greater DNA damage frequency following treatment with both PAT and OTA, when compared with the TK6 cell line. NH32 showed increased relative population doubling (RPD%) values representing the cell viability for all OTA and PAT treatment when compared to TK6. The increase in DNA damage frequency observed in a 10-day OTA treatment compared to a 24-hour treatment was not associated with TP53 deficiency. However, TP53 deficiency caused a decrease in the cytotoxic effects of both mycotoxins. Prolonged in vitro dosing may prove to be an effective approach to better characterise how xenobiotics damage DNA and cell viability, thereby identifying potential hazards to humans.