Lack of in vivo mutagenicity and oxidative DNA damage by flumequine in the livers of gpt delta mice.
Flumequine (FLU), an anti-bacterial quinolone agent, has been recognized as a non-genotoxic carcinogen for the mouse liver, but recent reports have suggested that some genotoxic mechanism involving oxidative DNA damage may be responsible for its hepatocarcinogenesis. In the present study, we investigated this possibility in the mouse liver using male and female B6C3F1 gpt delta mice fed diet containing 0.4% FLU, a carcinogenic dose, for 13 weeks. Measurements of 8-hydroxydeoxyguanosine levels in liver DNA, and gpt point and deletion mutations revealed no significant increases in any of these parameters in either sex. Histopathologically, centrilobular swelling of hepatocytes with vacuolation was apparent, however, together with significant increase in bromodeoxyuridine-labeling indices in the treated males and females. These results suggest that genotoxicity, including oxidative DNA damage, is not involved in mouse hepatocarcinogenesis by FLU, which might rather solely exert tumor-promoting effects in the liver.
Kuroiwa
Yuichi
Y
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Tokyo 158-8501, Japan.
Umemura
Takashi
T
Nishikawa
Akiyoshi
A
Kanki
Keita
K
Ishii
Yuji
Y
Kodama
Yukio
Y
Masumura
Ken-ichi
K
Nohmi
Takehiko
T
Hirose
Masao
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity; D001973:Bromodeoxyuridine / Q000032:analysis / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D024841:Fluoroquinolones / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007120:Immunochemistry; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009152:Mutagenicity Tests / Q000379:methods; D009154:Mutation; D009929:Organ Size / Q000187:drug effects; D010430:Pentosyltransferases / Q000235:genetics / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
D000890:Anti-Infective Agents; D029968:Escherichia coli Proteins; D024841:Fluoroquinolones; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D010430:Pentosyltransferases; C071962:Gpt protein, E coli; D001973:Bromodeoxyuridine; D003849:Deoxyguanosine; C012976:flumequine