title: Aflatoxin M1 cytotoxicity against human intestinal Caco-2 cells is enhanced in the presence of other mycotoxins.
abstract: Aflatoxin M1 (AFM1), a class 2B human carcinogen, is the only mycotoxin with established maximum residue limits (MRLs) in milk. Toxicological data for other mycotoxins in baby food, containing cereals and milk, either in isolation or in combination with AFM1, are sparse. The aim of this study was to investigate the cytotoxicity of AFM1, ochratoxin A (OTA), zearalenone (ZEA), and α-zearalenol (α-ZOL), individually and in combinations, in human Caco-2 cells. The tetrazolium salt (MTT) assay demonstrated that (i) OTA and AFM1 had similar cytotoxicity, which was higher than that of ZEA and α-ZOL, after a 72 h exposure; and (ii) the quaternary combination had the highest cytotoxicity, followed by tertiary and binary combinations and individual mycotoxins. Isobologram analysis indicated that the presence of OTA, ZEA, and/or α-ZOL with AFM1 led to additive and synergistic cytotoxicity in most combinations. The cytotoxicity of OTA was similar to that of AFM1, suggesting that OTA in food poses a health risk to consumers. Furthermore, AFM1 cytotoxicity increased dramatically in the presence of OTA, ZEA, and/or α-ZOL (p < 0.01), indicating that the established MRLs for AFM1 should be re-evaluated considering its frequent co-occurrence with other mycotoxins in baby food which contains milk and cereals.
authors.affiliation: Ministry of Agriculture Laboratory of Quality & Safety Risk Assessment for Dairy Products (Beijing), Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China.
authors.forename: Y N
authors.initials: YN
authors.lastname: Gao
authors.affiliation: Ministry of Agriculture Laboratory of Quality & Safety Risk Assessment for Dairy Products (Beijing), Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China.
authors.forename: J Q
authors.initials: JQ
authors.lastname: Wang
authors.affiliation: Ministry of Agriculture Laboratory of Quality & Safety Risk Assessment for Dairy Products (Beijing), Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China.
authors.forename: S L
authors.initials: SL
authors.lastname: Li
authors.affiliation: Ministry of Agriculture Laboratory of Quality & Safety Risk Assessment for Dairy Products (Beijing), Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China.
authors.forename: Y D
authors.initials: YD
authors.lastname: Zhang
authors.affiliation: Ministry of Agriculture Laboratory of Quality & Safety Risk Assessment for Dairy Products (Beijing), Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China. Electronic address: jiaqiwang@vip.163.com.
authors.forename: N
authors.initials: N
authors.lastname: Zheng
mesh_terms: D016607:Aflatoxin M1 / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D009183:Mycotoxins / Q000633:toxicity*; D011042:Poisons / Q000633:toxicity*; D014407:Tumor Cells, Cultured
chemical_list: D009183:Mycotoxins; D011042:Poisons; D016607:Aflatoxin M1
keywords: Co-contamination; Cytotoxicity; Human colon adenocarcinoma cells; Mycotoxin