Tumor-promoting activities of hydroquinone and 1,1-dimethylhydrazine after initiation of newborn mice with 1-methyl-1-nitrosourea.
To clarify the suitability of a newborn-mouse carcinogenesis assay to detect tumor-promoting activities of carcinogens, the non-genotoxic hydroquinone (HQ) and genotoxic 1,1-dimethylhydrazine (UDMH) were administered to mice during the promotion stage after treatment with 1-methyl-1-nitrosourea (MNU) (20 mg/kg body wt, single intraperitoneal injection) at day 9 after birth. Initiated males and females thus received either HQ at 0.8% in basal diet, or UDMH, at 20 mg/kg body wt once weekly by subcutaneous injection, from day 14 until the end of the experiment at 30 weeks of age. Uninitiated newborn mice, given an injection of the vehicle (0.01 M citrate buffer (pH 5.5), 20 mg/kg body wt), also received HQ or UDMH in the same way. Histopathologically, focal proliferative lesions were found in the livers of male mice and in the lungs of both male and female mice in the MNU-treated groups. HQ significantly increased the incidence and multiplicity of altered hepatocellular foci, the combined incidence of hepatocellular adenomas and carcinomas in males and the incidence and multiplicity of lung adenomas and the combined incidence of lung adenomas and carcinomas in female mice. In addition, four out of eleven MNU + HQ-treated male mice developed lung carcinomas, showing a significant elevation in multiplicity. UDMH also exhibited a tendency to increase the incidence and multiplicity of lung adenomas in female mice. Thus tumor-promoting effects of HQ or UDMH were apparently exerted in the target organs and the MNU-initiated two-stage newborn-mouse carcinogenesis assay may be useful for detection of genotoxic or non-genotoxic carcinogenicity.
Tamura
T
T
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
Shibutani
M
M
Toyoda
K
K
Shoda
T
T
Takada
K
K
Uneyama
C
C
Takahashi
M
M
Hirose
M
M
D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002277:Carcinoma / Q000139:chemically induced / Q000473:pathology; D004127:Dimethylhydrazines / Q000633:toxicity*; D005260:Female; D006873:Hydroquinones / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D009153:Mutagens / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects
D002273:Carcinogens; D004127:Dimethylhydrazines; D006873:Hydroquinones; D009153:Mutagens; C013958:dimazine; D008770:Methylnitrosourea; C031927:hydroquinone