Metallothionein modulates the carcinogenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine in mice.
We examined the carcinogenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in transgenic mice deficient in the metallothionein (MT) I and II genes and in control (129/Sv) mice. Both strains of mice were given BBN for 8 weeks with or without Zn treatment. All mice were killed at 12 weeks after the cessation of BBN administration. BBN induced bladder tumors in 75% of MT null mice and in 43% of 129/Sv mice. The average number of bladder tumors per mouse was significantly higher in MT null mice (1. 18 +/- 0.27) than in 129/Sv mice (0.43 +/- 0.20). Zn treatment suppressed the carcinogenicity of BBN in 129/Sv mice but not in MT null mice. Histopathological examination of the tumors revealed that the malignant potential of bladder tumors in 129/Sv mice was greater than that in MT null mice. These results indicate that MT is an important modulator of carcinogenicity of BBN in the bladder of mice.
Kondo
Y
Y
Department of Urology, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
Himeno
S
S
Endo
W
W
Mita
M
M
Suzuki
Y
Y
Nemoto
K
K
Akimoto
M
M
Lazo
J S
JS
Imura
N
N
D000818:Animals; D002085:Butylhydroxybutylnitrosamine / Q000494:pharmacology / Q000633:toxicity*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology*; D008668:Metallothionein / Q000172:deficiency / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D017967:Zinc Compounds / Q000494:pharmacology*
D002273:Carcinogens; D002712:Chlorides; D017967:Zinc Compounds; D002085:Butylhydroxybutylnitrosamine; C016837:zinc chloride; D008668:Metallothionein