Iwamoto Y, Ferguson L R, Pogai H B, Uzuhashi T, Kurita A, Yangihara Y, Denny W A
Department of Microbiology, School of Pharmaceutical Science, University of Shizuoka, Japan.
Mutat Res. 1992 Oct;280(4):233-44. doi: 10.1016/0165-1218(92)90053-3.
Analogues of amsacrine and other 9-anilinoacridines, bearing azide groups at various positions, were tested for their mutagenic activity in five strains of Salmonella typhimurium, both before and after photoirradiation. Azido substitution at the 2- or 3-position of the acridine or the 1'-position of the aniline led to compounds which were active frameshift mutagens, as detected in strain TA1537. Photoirradiation enhanced both the mutagenicity and the cytotoxicity of the azido compounds. Analogues bearing two azido groups at either the 2,6- or 3,6-positions were less strongly mutagenic in the dark, and light activation led to a toxic but only weakly mutagenic product. The effects of photoirradiation were decreased by aniline ring substitution, and were essentially eliminated by additional methyl substitution in the acridine ring. Comparison of events in TA1537 and TA98 suggested that photoirradiation of the 2- or 3-azido compounds gave a product which was capable of forming covalent bonds with DNA. The azide-containing analogues readily formed single strand DNA breaks on irradiation in the presence of DNA, but the efficiency of this reaction varied considerably.
对在不同位置带有叠氮基的安吖啶及其他9-苯胺基吖啶类似物，在光照射前后，于五种鼠伤寒沙门氏菌菌株中测试其诱变活性。吖啶的2-或3-位或苯胺的1'-位上的叠氮取代产生的化合物是活性移码诱变剂，如在TA1537菌株中检测到的那样。光照射增强了叠氮化合物的诱变性和细胞毒性。在2,6-或3,6-位带有两个叠氮基的类似物在黑暗中诱变活性较弱，光激活产生一种有毒但诱变活性很弱的产物。苯胺环取代降低了光照射的效果，吖啶环上额外的甲基取代基本消除了这种效果。TA1537和TA98中的情况比较表明，2-或3-叠氮化合物的光照射产生一种能够与DNA形成共价键的产物。含叠氮的类似物在有DNA存在的情况下照射时容易形成单链DNA断裂，但该反应的效率差异很大。
