title: DNA adduct formation by Fusarium culture extracts: lack of role of fusarin C.
abstract: Fusarium fungi have been shown to infect corn and other crops worldwide, and have a significant impact on human health through loss of crops or contamination of food with mycotoxins. Isolates of Fusarium fungi from an area of South Africa with high incidence of esophageal cancer have been shown to induce esophageal and liver cancer in rats. Several isolates of Fusarium fungi were grown on corn to determine if genotoxic products were produced. We report the incubation of methanol extracts of Fusarium verticillioides cultures with DNA in the presence of rat liver fractions (S9) resulted in the formation of a unique DNA adduct that was detected by (32)P-postlabeling. Fusarin C was purified from cultures of Fusarium verticillioides RRC 415, and was not responsible for the formation of the DNA adduct. Treatment of the methanolic extracts with ultraviolet B radiation reduced the fusarin C content in the extract; however, this had no effect on the formation of the DNA adduct following incubation of the extract with DNA and S9. The unique DNA adduct was formed following the incubation of several Fusarium verticillioides isolates from the US and South Africa, while extracts of cultures of Fusarium graminearium and Fusarium sacchari isolates formed very little of the DNA adduct when incubated with DNA and S9. These data suggest that neither fusarin C nor any of its metabolites are responsible for formation of the DNA adduct, and that an unidentified compound is present in F. verticillioides cultures that forms a DNA adduct, and may be important in the etiology of human esophageal cancer.
authors.affiliation: Division of Biochemical Toxicology, HFT-110, National Center for Toxicological Research, US Food and Drug Administration, US Public Health Service, 3900 NCTR Road, Jefferson, AR 72079-9205, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Bever
authors.forename: L H
authors.initials: LH
authors.lastname: Couch
authors.forename: J B
authors.initials: JB
authors.lastname: Sutherland
authors.forename: A J
authors.initials: AJ
authors.lastname: Williams
authors.forename: R D
authors.initials: RD
authors.lastname: Beger
authors.forename: M I
authors.initials: MI
authors.lastname: Churchwell
authors.forename: D R
authors.initials: DR
authors.lastname: Doerge
authors.forename: P C
authors.initials: PC
authors.lastname: Howard
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts / Q000096:biosynthesis*; D004355:Drug Stability; D005670:Fusarium / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D009183:Mycotoxins / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D011090:Polyenes / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D012474:Salmon; D014020:Tissue Extracts
chemical_list: D018736:DNA Adducts; D009183:Mycotoxins; D011090:Polyenes; D014020:Tissue Extracts; D004247:DNA; C041403:fusarin C