Beije B
Mutat Res. 1987 Apr;187(4):227-34. doi: 10.1016/0165-1218(87)90041-3.
The genotoxic activity of the benzidine-derived azo dye, Direct Black 38 (DB38), was studied in vivo, using two different genetic end-points: unscheduled DNA synthesis in liver (UDS) and bone marrow micronucleus (MN). Exposure times were 12, 24 or 36 h. Both assays were performed in the same rat, except for the 24-h exposure when only MN was investigated. For the liver UDS assay, the rat hepatocarcinogen, 6-dimethylaminophenylazobenzthiazole (6BT), was used as positive control and for the MN assay, cyclophosphamide (CP). In agreement with earlier results, 6BT gave rise to a dose-related increase in liver UDS after 12-h exposure to 25 or 50 mg/kg bw. After 36-h exposure, there was still an indication of a weak dose-response effect between 0 and 5 net nuclear grains (NG). DB38 induced liver UDS at the higher dose levels used (500 and 1000 mg/kg), and after both 12- and 36-h exposure. With the longer exposure time, a weak induction of UDS was also observed at 100 mg/kg. The strongest UDS induction (12.2 NG), was obtained in one rat after 36-h exposure to 500 mg/kg. DB38 also had a weak effect on the MN induction, which was statistically significant at the higher concentrations used. A dose-related response was observed at all exposure times used.
利用两种不同的遗传终点,即肝脏中的非程序性DNA合成(UDS)和骨髓微核(MN),在体内研究了联苯胺衍生的偶氮染料直接黑38(DB38)的遗传毒性活性。暴露时间为12、24或36小时。除了仅研究MN的24小时暴露外,两种试验均在同一只大鼠中进行。对于肝脏UDS试验,使用大鼠肝癌致癌物6-二甲基氨基苯基偶氮苯并噻唑(6BT)作为阳性对照,对于MN试验,使用环磷酰胺(CP)。与早期结果一致,6BT在以25或50mg/kg体重暴露12小时后,肝脏UDS出现剂量相关增加。暴露36小时后,在0至5个净核颗粒(NG)之间仍有弱剂量反应效应的迹象。DB38在使用的较高剂量水平(500和1000mg/kg)以及12小时和36小时暴露后均诱导肝脏UDS。暴露时间较长时,在100mg/kg也观察到UDS的弱诱导。在一只大鼠中,36小时暴露于500mg/kg后获得最强的UDS诱导(12.2NG)。DB38对MN诱导也有微弱影响,在使用的较高浓度下具有统计学意义。在所有使用的暴露时间均观察到剂量相关反应。