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Mutagenic activities of DAB and its impurities
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52 Sakamoto, K., N. Tanaka and S. Iwahara, Food and Drug Safety Center, Kanagawa (Japan) The ability of fetal liver microsomes of rats and mice to activate indirect mutagens in Salmonella mutagenicity test The ability of fetal liver microsomes to convert indirect mutagens into ultimate mutagens was measured by Salmonella mutagenicity test using strains TA100 and TA98. Sprague-Dawley rats and BDF t ( C 5 7 B L / 6 N > ( D B A / 2 ) mice in various pregnant stages were treated with PCB (500 mg/kg) at 72 h before sacrifice. Each of fetal and maternal liver $9 was prepared according to the method of B.N. Ames. Fetal $9 was less effective than maternal $9 in most mutagens tested. The metabolizing effect of fetal $9 from PCB-treated rats and mice on B[a]P could be detected on the day before birth, while that from untreated mothers could not be detected in any pregnant stages. In the case of Trp-p-2, a gradual increase in the activity during the 3 days before birth was observed for fetal $9 from both PCB-treated and untreated animals.
53 Sakamoto, Y., O. Nagayabu, K.S. Yamamoto and Y. Kikuchi, Central Research Division, Takeda Chemical Industries, Ltd., Osaka (Japan) Mutagenic activities of DAB and its impurities p-Dimethylaminoazobenzene (DAB) is often used as a positive control in the reversion test on E. coli WP2hcr with metabolic activation ($9 mix). In our experience, the mutagenic activity of DAB has varied from one sample to another depending upon its grade and commercial source. In this report, 10 different lots of DAB were tested for their mutagenicity using WP2hcr, and S. typhimurium TA1537, TA100, and TA98 with the $9 prepared from phenobarbital- and 13-naphthoflavone-induced rat liver. Seven of the 10 lots tested showed strong to weak mutagenic activities in at least one of the indicator strains; the other three
were not mutagenic. Using thin-layer chromatography, many impurities were isolated from the lots that showed mutagenicity. Some of the impurities were mutagenic, though the isolated DAB itself showed no mutagenicity in the same test system. On the other hand, all the DAB lots tested showed mutagenic activities in TA98 using Aroclor-induced $9; only these activities were strengthened by a co-mutagen, norharman. These results indicate that the mutagenic activity of DAB in WP2hcr is caused by impurities contained in some of the lots and not by DAB itself.
54 Namiki, K., M. Yamanaka, T. Osawa ~ and M. Namiki ~, Sugiyama Women's University and Nagoya University, Nagoya (Japan) Mutagenicity of spice-nitrite reaction products: on safrol analogues In the course of our systematic investigation of formation of mutagens by the spice nitrite reaction, we have observed that safrol is the main component to produce the mutagenic products by the reaction of nutmeg with nitrite. In order to determine the structure-activity relationship, 29 common safrol analogues were reacted with sodium nitrite and the mutagenicity was tested using S. (yphimurium TA100 and TA98. Strong mutagenicity was observed, especially, in the nitrite-treated safrol, isosafrol and piperonyl alcohol without metabolic activation, however, the nitrite-treated simple phenols were not mutagenic. These data indicated that propenyl and methylene dioxy groups are essential for mutagen formation and it is assumed that C-nitro type mutagens are likely to be formed by addition of nitrite to 1,3,4-trisubstituted aromatic rings of safrol analogues.
55 Negishi, C., M. Tsuda, K. Wakabayashi, S. Sato, T. Sugimura and M. J~rgerstad 1, National Cancer Center Research Institute, Tokyo (Japan) and 1 Lund University, Lund (Sweden)
52 Sakamoto, K., N. Tanaka and S. Iwahara, Food and Drug Safety Center, Kanagawa (Japan) The ability of fetal liver microsomes of rats and mice to activate indirect mutagens in Salmonella mutagenicity test The ability of fetal liver microsomes to convert indirect mutagens into ultimate mutagens was measured by Salmonella mutagenicity test using strains TA100 and TA98. Sprague-Dawley rats and BDF t ( C 5 7 B L / 6 N > ( D B A / 2 ) mice in various pregnant stages were treated with PCB (500 mg/kg) at 72 h before sacrifice. Each of fetal and maternal liver $9 was prepared according to the method of B.N. Ames. Fetal $9 was less effective than maternal $9 in most mutagens tested. The metabolizing effect of fetal $9 from PCB-treated rats and mice on B[a]P could be detected on the day before birth, while that from untreated mothers could not be detected in any pregnant stages. In the case of Trp-p-2, a gradual increase in the activity during the 3 days before birth was observed for fetal $9 from both PCB-treated and untreated animals.
53 Sakamoto, Y., O. Nagayabu, K.S. Yamamoto and Y. Kikuchi, Central Research Division, Takeda Chemical Industries, Ltd., Osaka (Japan) Mutagenic activities of DAB and its impurities p-Dimethylaminoazobenzene (DAB) is often used as a positive control in the reversion test on E. coli WP2hcr with metabolic activation ($9 mix). In our experience, the mutagenic activity of DAB has varied from one sample to another depending upon its grade and commercial source. In this report, 10 different lots of DAB were tested for their mutagenicity using WP2hcr, and S. typhimurium TA1537, TA100, and TA98 with the $9 prepared from phenobarbital- and 13-naphthoflavone-induced rat liver. Seven of the 10 lots tested showed strong to weak mutagenic activities in at least one of the indicator strains; the other three
were not mutagenic. Using thin-layer chromatography, many impurities were isolated from the lots that showed mutagenicity. Some of the impurities were mutagenic, though the isolated DAB itself showed no mutagenicity in the same test system. On the other hand, all the DAB lots tested showed mutagenic activities in TA98 using Aroclor-induced $9; only these activities were strengthened by a co-mutagen, norharman. These results indicate that the mutagenic activity of DAB in WP2hcr is caused by impurities contained in some of the lots and not by DAB itself.
54 Namiki, K., M. Yamanaka, T. Osawa ~ and M. Namiki ~, Sugiyama Women's University and Nagoya University, Nagoya (Japan) Mutagenicity of spice-nitrite reaction products: on safrol analogues In the course of our systematic investigation of formation of mutagens by the spice nitrite reaction, we have observed that safrol is the main component to produce the mutagenic products by the reaction of nutmeg with nitrite. In order to determine the structure-activity relationship, 29 common safrol analogues were reacted with sodium nitrite and the mutagenicity was tested using S. (yphimurium TA100 and TA98. Strong mutagenicity was observed, especially, in the nitrite-treated safrol, isosafrol and piperonyl alcohol without metabolic activation, however, the nitrite-treated simple phenols were not mutagenic. These data indicated that propenyl and methylene dioxy groups are essential for mutagen formation and it is assumed that C-nitro type mutagens are likely to be formed by addition of nitrite to 1,3,4-trisubstituted aromatic rings of safrol analogues.
55 Negishi, C., M. Tsuda, K. Wakabayashi, S. Sato, T. Sugimura and M. J~rgerstad 1, National Cancer Center Research Institute, Tokyo (Japan) and 1 Lund University, Lund (Sweden)