Enhancement by acrylamide of N-methyl-N-nitrosourea-induced rat mammary tumor development-possible application for a model to detect co-modifiers of carcinogenesis.
Acrylamide (AA) has recently been reported to be spontaneously formed in fried and baked foods with various concentrations. Although carcinogenicity in humans is as yet equivocal, numerous positive genotoxicity data in vitro and in vivo and results of rat long-term carcinogenicity studies demonstrating tumor induction at multiple sites, like the mammary gland, thyroid and testes, suggest the risk with dietary exposure may not be negligible. In the present study, to establish a medium-term carcinogenesis model for screening of agents with the potential to modify AA effects on the mammary gland and thyroid, we pretreated rats with 7,12-dimethylbenz(a)anthracene (DMBA), in combination with N-bis(2-hydroxypropyl)nitrosamine (DHPN), or N-methyl-N-nitrosourea (MNU) alone and then administered AA at 20 and 40 ppm in the drinking water for 30 weeks. The incidence and multiplicity of mammary tumors were increased at the high dose (P<0.05) in MNU- but not DMBA+DHPN-treated rats. No thyroid tumors were induced in any case. The results indicate that the MNU model is suitable for detection of modifiers of AA actions.
Imai
Toshio
T
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-Ku, Tokyo 158-8501, Japan. imai@nihs.go.jp
Cho
Young-Man
YM
Hasumura
Mai
M
Hirose
Masao
M
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D020106:Acrylamide / Q000633:toxicity*; D000284:Administration, Oral; D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced* / Q000503:physiopathology; D008770:Methylnitrosourea / Q000633:toxicity*; D009602:Nitrosamines / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013964:Thyroid Neoplasms / Q000503:physiopathology
D000477:Alkylating Agents; D002273:Carcinogens; D009602:Nitrosamines; D020106:Acrylamide; C012457:diisopropanolnitrosamine; D015127:9,10-Dimethyl-1,2-benzanthracene; D008770:Methylnitrosourea