Hemoglobin adduct and hepatic- and urinary bladder-DNA adduct levels in rapid and slow acetylator Syrian inbred hamsters administered 2-aminofluorene.
The levels of covalently bound arylamine-hemoglobin and DNA adduct formation were used as dosimeters to measure the effect of acetylator genotype and sex on the metabolic conversion of the carcinogen, 2-aminofluorene, to reactive intermediates. A single high dose of 2-aminofluorene (60 mg/kg b.wt. i.p.) was administered to male and female homozygous rapid (Patr/Patr) acetylator hamsters (MHA/SsLaK) and homozygous slow (Pats/Pats) acetylator hamsters (Bio. 82.73/H). By using 32P-postlabeling assay methodology, a sole nonacetylated DNA adduct, which cochromatographed with authentic N-(deoxyguanosin-8-yl)-2-aminofluorene was detected at 3, 6, 12, 18 or 24 hr postdosing in liver and urinary bladder DNA of both rapid and slow acetylator hamsters. The highest levels were detected at 18 hr post 2-aminofluorene injection at which time the average levels of hepatic 2-aminofluorene-DNA adducts were similar between male and female rapid and slow acetylators. By comparison, the levels of 2-aminofluorene-DNA adducts in the urinary bladder at 18 hr were about 4-fold lower than in the liver, and were significantly greater in homozygous rapid than in homozygous slow acetylator counterparts (P less than .01). In both the liver and urinary bladder, the levels of 2-aminofluorene-DNA adducts were independent of sex. In contrast to the DNA adduct data, the levels of 2-aminofluorene-hemoglobin adducts, evaluated by capillary gas chromatography-mass spectrometry, were significantly higher in the homozygous slow acetylators than in homozygous rapid acetylators. However, there again were no differences between males and females.(ABSTRACT TRUNCATED AT 250 WORDS)
Flammang
T J
TJ
Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, Arkansas.
Yerokun
T
T
Bryant
M S
MS
Couch
L H
LH
Kirlin
W G
WG
Lee
K J
KJ
Ogolla
F
F
Ferguson
R J
RJ
Talaska
G
G
Hein
D W
DW
D000107:Acetylation; D000818:Animals; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D005449:Fluorenes / Q000633:toxicity*; D008401:Gas Chromatography-Mass Spectrometry; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism*; D006720:Homozygote; D008099:Liver / Q000187:drug effects*; D008297:Male; D008647:Mesocricetus / Q000235:genetics; D009153:Mutagens / Q000633:toxicity*; D001743:Urinary Bladder / Q000187:drug effects*
D005449:Fluorenes; D006454:Hemoglobins; D009153:Mutagens; C012177:2-aminofluorene; D004247:DNA