Fusarium moniliforme metabolites: genotoxicity of culture extracts.
Fusarin C (FC) is a potent mutagen which has been isolated from Fusarium moniliforme culture extracts (FME). We have confirmed that the mutagenicity of these extracts is enhanced by phenobarbital- or Aroclor-induced microsomes and shown that: (i) additional, direct-acting, mutagens are present in crude extracts from F. moniliforme cultures; (ii) Salmonella typhimurium TA 100 exposed to FME in the presence of S9 mixtures shows an increased number of DNA strand breaks as detected by intercalation of ethidium bromide; (iii) exposure of polyoma-transformed rat fibroblast cells to HPLC-purified FC induced asynchronous replication of polyoma DNA sequences, a phenomenon also observed when these cells were exposed to a variety of other carcinogens; (iv) FME can alkylate 4-(p-nitrobenzyl)pyridine in the absence of S9 mix, although less efficiently than styrene oxide; and (v) these additional direct-acting mutagens, present in crude extracts from F. moniliforme cultures, may be responsible for the DNA adducts formed by reaction with calf thymus DNA in the absence of metabolic activation and detected by the 32P-postlabeling assay. All of these observations suggest that significant health effects may be associated with human exposure to F. moniliforme and that further studies on its metabolites are needed.
Lu
S J
SJ
Department of Chemical Etiology and Carcinogenesis, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Ronai
Z A
ZA
Li
M H
MH
Jeffrey
A M
AM
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects; D005670:Fusarium / Q000472:pathogenicity*; D066298:In Vitro Techniques; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D011090:Polyenes / Q000633:toxicity*; D011120:Polyomavirus / Q000254:growth & development
D009153:Mutagens; D011090:Polyenes; C041403:fusarin C