Induction of DNA single-strand breaks and DNA synthesis inhibition in CHO and AWRF cells after exposure to sterigmatocystin and penicillic acid.

Sterigmatocystin is 12 times more toxic to transformed rat fibroblasts (AWRF) than to Chinese hamster ovary cells (CHO). In contrast, penicillic acid is twice more toxic to CHO cells than to AWRF cells. The ability of sterigmatocystin and penicillic acid to inhibit DNA synthesis correlated well with the differences in cytotoxicity of these mycotoxins in the cell lines used. Sterigmatocystin at a concentration of 10 micrograms/ml inhibited DNA synthesis in AWRF cells during a 3-h exposure to 60% of that found in controls, but did not inhibit DNA synthesis in CHO cells. Within the same time interval penicillic acid inhibited DNA synthesis in AWRF cells at concentrations higher than 5 micrograms/ml and in CHO cells at concentrations over 0.5 microgram/ml. Induction of DNA single-strand breaks (SSB) during a 3-h exposure to sterigmatocystin and penicillic acid was comparable in both cell types. The results suggest that sterigmatocystin is metabolized to reactive metabolites that are responsible for the toxicity and DNA synthesis inhibition at a more rapid rate in AWRF cells than in CHO cells. The observed ability to induce SSB indicates that penicillic acid is potentially carcinogenic.