| Autor: |
Babu, Satram R., Lakshmi, Vijaya M., Hsu, F.F., Zenser, Terry V., Davis, Bernard B. |
| Zdroj: |
Carcinogenesis; 1992, Vol. 13 Issue 7, p1235-1240, 6p |
| Abstrakt: |
The mechanism by which benzidine induces bladder cancer in dog was evaluated by assessing me tabolism of [H]benzidine by dog liver slices and microsomes. Slices incubated with 0.05 mM [H]benzidine exhibited a 32.5 min peak, which was also produced when microsomal incubations were supplemented with UDP-glucuronic acid. In contrast to microsomes, very little of the 32.5 min peak was produced with the 100 000 g supernatant fraction. Microsomal metabolism was increased 5-fold by pretreatment with Triton X-100. Very little activity was observed with rat microsomes in either the presence or absence of Triton X-100. This metabolite was also generated by incubating benzidine with glucuronk add at 4°C for 3 days. Thermospray MS identified this metabolite as benzidine -glucuronide. At 37°C, the t stability of purified -glucuronide was 99, 25 and 3 min in dog urine adjusted to pH 7.3, 6.3 and 5.3 respectively. The -glucuronide was quite stable at pH 9.3, in dog plasma, and in aprotic solvents for 4 h at 37°C. Relative to benzidine, its -glucuronide is weakly bound to plasma proteins but not more reactive with DNA. Thus, detoxification by liver provides a mechanism for accumulation of benzidine in acidic urine, uptake of benzidine into bladder epithelium, and activation of benzidine in bladder. The liver and -glucuronidation play a potentially important role in the species specificity of benzidine carcinogenesis. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
