Intestinal microflora enhances formation of DNA adducts following administration of 2-NF and 2-AAF.
2-Nitrofluorene (NF) is found in the environment mainly due to incomplete combustion, as in vehicles. The major class of metabolites in vivo in rats after oral administration is the reduced and acetylated metabolites, e.g. derivatives of 2-acetylaminofluorene (AAF). The intestinal microflora reduces the nitro function to an amine which is further metabolized via acetylation and hydroxylations. In this study, NF and AAF were orally administered to germ-free and conventional rats with the aim of studying DNA adduct formation in different tissues with the 32P-post-labelling assay. Chromatographic detection was performed with TLC and on-line 32P detection after HPLC separation of DNA adducts. The major (95%) DNA adduct formed was dG-C8-AF for both NF and AAF. The potency to form DNA adducts successively declined with the combinations conventional/AAF, germ-free/AAF, conventional/NF and germ-free/NF. The DNA adduct dG-C8-AF was detected in all four tissues that were analysed, e.g. liver, kidney, lung and heart. The presence of intestinal microflora enhanced the formation of DNA adducts in the tissues studied.
Möller
L
L
Center for Nutrition and Toxicology, Karolinska Institute, Huddinge, Sweden.
Zeisig
M
M
Midtvedt
T
T
Gustafsson
J A
JA
D015073:2-Acetylaminofluorene / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004247:DNA / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005449:Fluorenes / Q000378:metabolism / Q000633:toxicity*; D005856:Germ-Free Life; D007422:Intestines / Q000187:drug effects / Q000382:microbiology*; D007553:Isotope Labeling; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains
D005449:Fluorenes; D010761:Phosphorus Radioisotopes; C019499:2-nitrofluorene; D004247:DNA; D015073:2-Acetylaminofluorene