Metallothionein modulates the carcinogenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine in mice

We examined the carcinogenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine (B BN) 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 we eks with or without Zn treatment. All mice were killed at 12 weeks after th e 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 p er mouse was significantly higher in MT null mice (1.18 +/- 0.27) than in 1 29/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 o f 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 m ice.