Selective 8-hydroxyguanine formation in pancreatic DNA due to a single intravenous administration of 4-hydroxyaminoquinoline 1-oxide in rats.
8-Hydroxyguanine (8-OHG) formation, a possible initiating event, was determined in pancreatic and liver DNA and compared with the genesis of acinar cell and hepatocyte necrosis in male Wistar rats given a single intravenous administration of 4-hydroxyaminoquinoline 1-oxide (4-HAQO). At the non-necrotic but tumorigenic dose of 7.0 mg/kg body weight, 8-OHG was selectively generated in pancreatic DNA, in the absence of acinar cell necrosis, at the 6 and 24 h time points and repaired by the 48 h time point. When rats were exposed to 4-HAQO at a necrotic dose of 14.0 mg/kg body weight, 8-OHG was also selectively formed in pancreatic DNA with the same time-dependence of generation and repair, while acinar cell necrosis became evident at the 24 h time point and progressed thereafter. Whereas no hepatocyte necrosis was detected in any rats, 8-OHG values for liver DNA merely expressed slight increases only at the 24 and 48 h time points in rats given 14.0 mg/kg body weight of 4-HAQO. The present data suggest that formation of oxidative DNA damage, assayed by 8-OHG, in pancreatic DNA is independent from toxicity and may be involved, along with quinoline adducts, in mutational events underlying 4-HAQO-induced rat acinar cell carcinogenesis.
Nakae
D
D
Department of Oncological Pathology, Nara Medical University, Japan.
Andoh
N
N
Mizumoto
Y
Y
Endoh
T
T
Shimoji
N
N
Horiguchi
K
K
Shiraiwa
K
K
Tamura
K
K
Denda
A
A
Konishi
Y
Y
D015108:4-Hydroxyaminoquinoline-1-oxide / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000097:blood; D000681:Amylases / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004247:DNA / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008049:Lipase / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D015108:4-Hydroxyaminoquinoline-1-oxide; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008049:Lipase; D000681:Amylases