Failure of catalase to protect against aflatoxin B1-induced mouse lung tumorigenicity

The carcinogenic mycotoxin aflatoxin B1 (AFB1) induces 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation in mouse lung, an effect that can be prevented by treatment with polyethylene glycol-conjugated catalase (PEG-CAT). G → T transversion mutation in K-ras, an early event in AFB1-induced mouse lung carcinogenesis, is thought to result from AFB1-8,9-exo-epoxide binding to DNA to form AFB1-N7-guanine, but may also result from formation of 8-OHdG. Therefore, oxidative DNA damage may be important in AFB1 carcinogenicity. The objective of this study was to determine whether PEG-CAT would prevent AFB1 tumorigenicity. Mouse lung tumorigenesis was assessed following treatment of female A/J mice with 300 kU/kg PEG-CAT ip and/or 50 mg/kg AFB1. Mice were killed 7 months post-treatment and tumors greater than 1 mm in diameter were excised. Unexpectedly, the mean number of tumors per mouse in the PEG-CAT + AFB1 group (8.81 ± 3.64, n = 47) was greater than that of the group treated with AFB1 alone (7.05 ± 3.45, n = 42) (P < 0.05). The tumors obtained from mice treated with PEG-CAT + AFB1 were larger than those from mice treated with AFB1 alone (P < 0.05). There was no difference in K-ras exon 1 mutation spectrum or in the histological diagnosis of tumors between AFB1 and PEG-CAT + AFB1 groups (P > 0.05). In vitro incubation with mouse liver catalase (CAT) resulted in conversion of [3H]AFB1 into a DNA-binding species, a possible explanation for the results observed in vivo. These results demonstrate that PEG-CAT is not protective against AFB1 carcinogenicity in mouse lung despite preventing DNA oxidation.