A comparison of covalent DNA binding of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in respiratory tissues from human, rat and mouse.
In vivo and in vitro covalent DNA binding was investigated in an attempt to explain the higher susceptibility of A/J mouse lung and Fischer-344 rat trachea to 7,12-dimethylbenz[a]anthracene (DMBA) as compared to benzo[a]pyrene (BP), and to evaluate the relative susceptibility of the human respiratory tract to these compounds. After in vivo administration of either BP or DMBA to A/J mice covalent DNA binding was higher in the liver than in the lungs. Forty-eight hours after administration, but not before, binding of DMBA was higher than that of BP in both organs. In vitro studies using cultured explants of both human and A/J mouse peripheral lung, as well as human bronchus and Fischer-344 rat trachea, revealed that covalent DNA binding of DMBA to mouse lung and rat trachea were similar and that both were significantly higher than that of BP to these organs. Binding of BP and DMBA was similar in both human tissues and did not differ from BP binding in the animal tissues. Enzymatic hydrolysis and HPLC separation of the DNA-hydrocarbon adducts revealed that patterns of adducts in human and mouse peripheral lung were similar and qualitatively resembled known patterns in other target and non-target tissues. It is concluded that the higher susceptibility of the mouse lung and rat trachea to DMBA as compared to BP may be related to the higher covalent DNA binding of the former and that the relative carcinogenic risk of the human respiratory tract after exposure to DMBA may be the same as that after BP exposure.
Stoner
G D
GD
Schut
H A
HA
Daniel
F B
FB
Dixit
R
R
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism*; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D012137:Respiratory System / Q000378:metabolism*; D014132:Trachea / Q000378:metabolism
D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA