1-Hydroxypyrene as an indicator of the mutagenicity of coal tar after activation with human liver preparations.
Liver S9 fractions were prepared from male Wistar rats, either non-induced or induced with Aroclor 1254 and from 5 human kidney transplant donors. The preparations were compared for their ability to metabolize the premutagens present in coal tar to mutagenic metabolites in the Salmonella mutagenicity assay towards strain TA98. Low levels of mutagenicity of coal tar were seen with human S9 preparations. The differences between the S9 mix of the 5 donors in capacity to activate premutagens were approximately 6-fold. The activation of coal tar by rat liver S9 preparations was higher than by the human S9 preparations. The metabolic conversion of pyrene in coal tar to 1-hydroxypyrene by the same human S9 preparations was determined in a parallel assay. 3 human preparations showed a high correlation between the formation of 1-hydroxypyrene and bioactivation of coal tar to mutagenic metabolites. The slope values of the individual regression lines were equal, suggesting that 1-hydroxypyrene is a good indicator for the activation of premutagens present in coal tar.
Jongeneelen
F J
FJ
Department of Toxicology, Faculty of Medicine, University of Nijmegen, The Netherlands.
vd Akker
W
W
Bos
R P
RP
Anzion
R B
RB
Theuws
J L
JL
Roelofs
H M
HM
Henderson
P T
PT
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D020111:Chlorodiphenyl (54% Chlorine); D003033:Coal Tar / Q000378:metabolism* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000032:analysis; D011721:Pyrenes / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D001140:Aroclors; D011083:Polycyclic Compounds; D011721:Pyrenes; D020111:Chlorodiphenyl (54% Chlorine); D003033:Coal Tar; D003577:Cytochrome P-450 Enzyme System; C033146:1-hydroxypyrene