Parp-1 deficiency does not increase the frequency of tumors in the oral cavity and esophagus of ICR/129Sv mice by 4-nitroquinoline 1-oxide, a carcinogen producing bulky adducts.
The impact of poly(ADP-ribose) polymerase-1 (Parp-1)-deficiency on 4-nitroquinoline 1-oxide (4NQO)-induced carcinogenesis was studied in mice with an ICR/129Sv mixed genetic background. Parp-1(+/+), Parp-1(+/-) and Parp-1(-/-) animals given 4NQO for thirty-two weeks at 0.001% in their drinking water developed papillomas and squamous cell carcinomas of the tongue, palate and esophagus, but with no statistically significant variation with the Parp-1 genotype. Thus Parp-1 deficiency does not elevate susceptibility to carcinogenesis induced by a carcinogen which gives rise to bulky DNA lesions. This study also indicated that the ICR/129Sv mixed genetic background is associated with high yield induction of esophageal tumors by 4NQO.
Gunji
Akemi
A
Biochemistry Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Uemura
Akiko
A
Tsutsumi
Masahiro
M
Nozaki
Tadashige
T
Kusuoka
Osamu
O
Omura
Ken
K
Suzuki
Hiroshi
H
Nakagama
Hitoshi
H
Sugimura
Takashi
T
Masutani
Mitsuko
M
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004938:Esophageal Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009062:Mouth Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000502:physiology*
D002273:Carcinogens; D015112:4-Nitroquinoline-1-oxide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases