Formation of DNA adducts from 1-hydroxymethylpyrene in liver cells in vivo and in vitro.
The binding of 1-hydroxymethylpyrene (HMP) and its active metabolites, 1-hydroxymethylpyrene sulfate (SMP) and 1-chloromethylpyrene (CMP), to DNA was studied. In the liver of rats, maximum adduct levels were observed 1.5 h after i.p. injection of HMP, followed by a relatively rapid decrease. Separate exposure of different liver cell types in vitro to HMP led to high adduct levels in parenchymal cells, intermediate levels (1/10) in endothelial cells and low levels (1/200) in Kupffer cells. The adduct patterns were similar in the different cell types. The same pattern was also obtained when isolated DNA was incubated with SMP or CMP. One of the four major spots co-chromatographed on TLC with a dG adduct, one with a dA adduct and one with both dG and dA adducts. The fourth spot did not co-chromatograph with any of the adducts observed in reactions with any nucleic acid homopolymer.
Monnerjahn
S
S
Institut für Toxikologie, Universität Mainz, Germany.
Seidel
A
A
Steinberg
P
P
Oesch
F
F
Hinz
M
M
Stezowsky
J J
JJ
Hewer
A
A
Phillips
D H
DH
Glatt
H R
HR
D000818:Animals; D001483:Base Sequence; D001711:Biotransformation; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010761:Phosphorus Radioisotopes; D011089:Polydeoxyribonucleotides / Q000737:chemistry; D011721:Pyrenes / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism
D010761:Phosphorus Radioisotopes; D011089:Polydeoxyribonucleotides; D011721:Pyrenes; D004247:DNA; C065833:1-hydroxymethylpyrene