Sera N, Fukuhara K, Miyata N, Tokiwa H
Fukuoka Institute of Health and Environmental Science, Dazaifu, Fukuoka, Japan.
Mutagenesis. 2001 May;16(3):183-7. doi: 10.1093/mutage/16.3.183.
Nitro-azabenzo[a]pyrenes, 1- or 3-nitro-azabenzo[a]pyrene and their N-oxides are nitrated derivatives of azabenzo[a] pyrene (ABP) containing nitrogen in the 6-position of benzo[a]pyrene (B[a]P). The nitro-ABP-N-oxides (ABPOs) were formed by reaction of ABP with excess HNO(3). These derivatives were noteworthy as potent mutagens for Salmonella strains, and were present in fine particles of diesel particulates. In this study, micronucleus induction in mice and chromosomal aberrations due to means of Chinese hamster lung fibroblast (CHL) cells were investigated to determine genotoxicity in order to define the relationship with the mutagenic potency of these derivatives. The induction of micronucleus polychromatic erythrocytes (MNPCEs) was dependent on the dose response of 10-40 mg for 3-N-6-ABP, and of 10-40 mg for 1-N-6-ABP, and in addition, 1- and 3-N-6-ABPOs markedly induced MNPCEs in a dose range of 10-400 mg and from 1 to 80 mg, respectively, when the compound was intraperitoneally administrated in two mice at each dose. The results show that of the four compounds, 3-N-6-ABPO demonstrated a marked increase in MNPCES: On the other hand, chromosomal aberrations of the four compounds were investigated by the duplicate tests using CHLS: The results after a 48 h treatment induced aberrations of the chromatid type, chromatid breaks and exchanges for 1- and 3-N-6-ABP, and mainly chromatid exchanges for 1- and 3-N-6-ABPO. The frequency of chromosomal aberrations associated with nitro substitution on the ABPO structure. Chromosomal aberrations of nitro derivatives of ABPO substituted at the 3-position on the structure were more potent than those at the 1-postion. N-oxide derivatives have been found to be reduced to anion radicals much more easily than azaB[a]P and its nitro derivatives. This suggests that the electrochemical reduction of the chemicals plays an important role in the metabolic activation of nitrated B[a]P derivatives.
硝基氮杂苯并[a]芘、1-或3-硝基氮杂苯并[a]芘及其N-氧化物是氮杂苯并[a]芘（ABP）的硝化衍生物，在苯并[a]芘（B[a]P）的6位含有氮。硝基-ABP-N-氧化物（ABPOs）是通过ABP与过量硝酸（HNO₃）反应形成的。这些衍生物作为沙门氏菌菌株的强效诱变剂而值得关注，并且存在于柴油颗粒的细颗粒中。在本研究中，研究了小鼠体内的微核诱导以及中国仓鼠肺成纤维细胞（CHL）细胞导致的染色体畸变，以确定遗传毒性，从而确定这些衍生物的诱变效力之间的关系。多染性红细胞微核（MNPCEs）的诱导取决于3-N-6-ABP剂量为10至40毫克以及1-N-6-ABP剂量为10至40毫克时的剂量反应，此外，当以每剂量给两只小鼠腹腔注射化合物时，1-和3-N-6-ABPOs分别在10至400毫克和1至80毫克的剂量范围内显著诱导MNPCEs。结果表明，在这四种化合物中，3-N-6-ABPO显示出MNPCEs显著增加：另一方面，使用CHLS通过重复试验研究了这四种化合物的染色体畸变：48小时处理后的结果诱导了1-和3-N-6-ABP的染色单体型畸变、染色单体断裂和交换，以及1-和3-N-6-ABPO的主要染色单体交换。染色体畸变与ABPO结构上的硝基取代有关。结构上3位被取代的ABPO硝基衍生物的染色体畸变比1位被取代的更有效。已发现N-氧化物衍生物比氮杂B[a]P及其硝基衍生物更容易还原为阴离子自由基。这表明这些化学物质的电化学还原在硝化B[a]P衍生物的代谢活化中起重要作用。
