Organ-specific genotoxicity of the potent rodent colon carcinogen 1,2-dimethylhydrazine and three hydrazine derivatives: difference between intraperitoneal and oral administration.
We used a modification of the alkaline single cell gel electrophoresis (SCG) (Comet) assay to test the in vivo genotoxicity of four hydrazine derivatives--1,2-dimethylhydrazine (SDMH), 1,1-dimethylhydrazine (UDMH), hydrazine (HZ), and procarbazine (PCZ)--in mouse liver, lung, kidney, brain, and bone marrow, and in the mucosa of stomach, colon, and bladder. Mice were sacrificed 3 and 24 h after intra-peritoneal (i.p.) and oral (p.o.) administration. SDMH at 20 mg/kg i.p. yielded statistically significant DNA damage in all tested organs except for lung. In the gastrointestinal tract, SDMH was genotoxic in the stomach and the colon after i.p. treatment but only in the colon after 20 and 30 mg/kg p.o. treatment. UDMH at 50 mg/kg i.p. yielded DNA damage in the liver and lung at 3 h. PCZ at 200 mg/kg i.p. caused DNA damage in the liver, kidney, lung, brain, and bone marrow. UDMH and PCZ were positive in the stomach and colon p.o. but not by i.p. treatment. HZ at 100 mg/kg yielded DNA damage in the stomach, liver, and lung when given i.p. and in the brain when p.o. Thus, the administration route is important when evaluating organ-specific genotoxicity in multiple organs.
Laboratory of Genotoxicity, Faculty of Chemical and Biological Engineering, Hachinohe National College of Technology, Aomori, Japan. yfsasaki-c@hachinohe-ct.ac.jp
Y F
YF
Sasaki
A
A
Saga
M
M
Akasaka
S
S
Ishibashi
K
K
Yoshida
Y Q
YQ
Su
N
N
Matsusaka
S
S
Tsuda
D019813:1,2-Dimethylhydrazine / Q000008:administration & dosage / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D003106:Colon / Q000187:drug effects*; D004249:DNA Damage; D004127:Dimethylhydrazines / Q000008:administration & dosage / Q000633:toxicity*; D006834:Hydrazines / Q000008:administration & dosage / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D011344:Procarbazine / Q000008:administration & dosage / Q000633:toxicity*
D002273:Carcinogens; D004127:Dimethylhydrazines; D006834:Hydrazines; C029424:hydrazine; D011344:Procarbazine; C013958:dimazine; D019813:1,2-Dimethylhydrazine