Lung as a new target in rats of 2-amino-3-methylimidazo[4,5-f]quinoline carcinogenesis: results of a two-stage model initiated with N-bis(2-hydroxypropyl)nitrosamine.
The effects of IQ on the promotion stage of DHPN-induced lung carcinogenesis and contributions of oxidative stress were investigated in rats. Groups of 20 male 6-week-old F344 rats were given 0.1% DHPN in their drinking water for 2 weeks for initiation. From the age of 9 weeks, they were treated with 0, 150 and 300 p.p.m. of IQ in the diet for 27 weeks. Control rats were similarly fed 300 p.p.m. IQ or basal diet alone without the preceding initiation. IQ clearly (P < 0.01) enhanced the multiplicity of lung tumors in a dose-dependent manner (DHPN alone, 3.63 +/- 1.80; DHPN +150 p.p.m. IQ, 11.50 +/- 5.04; DHPN +300 p.p.m. IQ, 18.83 +/- 4.58 [no./rat]). In addition, the incidence of lung tumors in the 300 p.p.m. IQ alone group (25%) was significantly (P < 0.05) higher than that in the non-treatment group (0%). In a second experiment, male rats were given IQ at doses of 0 and 300 p.p.m. in the diet for one week in order to analyze 8-OHdG formation, levels of TBARS and BrdU-LI in the lungs. There were no changes in 8-OHdG or TBARS levels, but significant elevation of BrdU-LI occurred in the IQ administration group. The overall data clearly indicate that IQ is a potent lung carcinogen in rats, in which oxidative stress may not be involved in lung carcinogenesis.
Kitamura
Yasuki
Y
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Umemura
Takashi
T
Kanki
Keita
K
Ishii
Yuji
Y
Kuroiwa
Yuichi
Y
Masegi
Toshiaki
T
Nishikawa
Akiyoshi
A
Hirose
Masao
M
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004195:Disease Models, Animal; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011804:Quinolines / Q000633:toxicity*; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism
D002273:Carcinogens; D009602:Nitrosamines; D011804:Quinolines; D017392:Thiobarbituric Acid Reactive Substances; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C012457:diisopropanolnitrosamine; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D001973:Bromodeoxyuridine