Potent tumorigenicity of 7-chlorobenz[a]anthracene and 7-bromobenz[a]anthracene in the neonatal B6C3F (1) male mouse.
The tumorigenicity of 7-chlorobenz[a]anthracene (7-Cl-BA, and environmental contaminant, and 7 bromobenz[a]anthracene (7-Br-BA) was determines in the male B6C3F(1) newborn mouse. Mice receiving 7-Cl-BA and 7-Br-BA by i.p. injections at a dose of 1600 nmol per mouse on 1, 8, and 15 days after birth developed 92 and 96% hepatocellular adenomas, and 100 and 83% hepatocellular carcinoma, respectively. Metabolism by liver microsomes of 15-day-old mice each produced the corresponding trans-3,4-dihydrodiol. Analysis by (32)P-postlabeling/HPLC indicated the presence of DNA adducts derived from 7-Cl-BA trans-3,4-dihydrodiol and 7-Br-BA trans-3,4-dihydrodiol. Our results indicate that both 7-Cl-BA and 7-Br-BA are potent carcinogens and that bay-region diol epoxides are the ultimate metabolites that lead to DNA adduct formation and tumor initiation.
Fu
P P
PP
Department of Biochemical Toxicology, National Center for Toxicological Research, AR 72079, USA.
Von Tungeln
L S
LS
Zhan
D J
DJ
Bucci
T
T
D000818:Animals; D000831:Animals, Newborn; D000873:Anthracenes / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D001551:Benz(a)Anthracenes / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D001711:Biotransformation; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D018736:DNA Adducts / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms
D000873:Anthracenes; D001551:Benz(a)Anthracenes; D002273:Carcinogens; D018736:DNA Adducts; C046094:7-chlorobenz(a)anthracene; C038901:7-bromobenzanthracene