Harnasch D, Stumpf R
Mutat Res. 1984 May;126(3):279-95. doi: 10.1016/0027-5107(84)90008-3.
This work continues earlier studies concerning the use of histocompatibility mutations in mammalian germ cells as a mutagenicity test system (H test). The rate of spontaneous H mutations was re-examined using a new basis for the classification of H mutants. This procedure led to very high frequencies of suspected spontaneous H mutants: among C57Bl/6 mice, 6% and among C3H mice, 9%. F2 hybrids of a cross between these strains revealed 1% suspected H mutants. Using the same procedure, the sensitivity of the H test was examined with the mutagens ethylnitrosourea, benzo[a]pyrene, 2-acetylaminofluorene (2-AAF), with the solvent dimethyl sulfoxide (DMSO) and with the antibacterial nitrofurantoin. It was possible to demonstrate the mutagenic potential of all mutagens tested as well as their specific action on the different stages of male germ cell development. We succeeded in demonstrating the mutagenicity of 2-AAF for the first time in germ cells of a mammal. In contrast to the negative result with benzopyrene (BP) in the specific locus test, BP induced H mutants even at the very low dose of 2 mg/kg. DMSO was found to induce H mutations in spermatogonia. This extraordinary result is possibly due to the virus-inducing properties of this compound. Nitrofurantoin which is often used in treating bacterial infections of the urinary tract in humans showed a very stage-specific action on maturing spermatids. The value of the H test for mutagenicity testing is discussed with respect to its sensitivity and economy. The very high spontaneous frequency of suspected H mutants and the ease of inducing increased mutant frequencies by mutagens and by DMSO suggest the possibility that the majority of the histoincompatibilities found in the H test are due to induced antigenic gene products of endogenous viruses. This, however, does not interfere with the applicability of the H test for mutagenicity testing, but rather seems to augment its sensitivity to alkylating mutagens as well as mutagens which probably cause frameshift mutations. Other tests for mutations and/or inherited tumor proneness using mouse germ cells can easily be combined with the H test, because the test animal does not have to be killed, thus reducing the cost of the test.
这项工作延续了早期关于将组织相容性突变用于哺乳动物生殖细胞作为致突变性测试系统（H 测试）的研究。使用一种新的 H 突变体分类依据重新检查了自发 H 突变的发生率。该程序导致疑似自发 H 突变体的频率非常高：在 C57Bl/6 小鼠中为 6%，在 C3H 小鼠中为 9%。这两个品系杂交产生的 F2 杂种显示出 1%的疑似 H 突变体。使用相同程序，用诱变剂乙基亚硝基脲、苯并[a]芘、2-乙酰氨基芴（2-AAF）、溶剂二甲基亚砜（DMSO）以及抗菌药物呋喃妥因检测了 H 测试的敏感性。可以证明所有测试诱变剂的诱变潜力以及它们对雄性生殖细胞发育不同阶段的特定作用。我们首次成功证明了 2-AAF 在哺乳动物生殖细胞中的诱变性。与苯并芘（BP）在特定基因座测试中的阴性结果相反，BP 即使在 2 mg/kg 的极低剂量下也能诱导 H 突变体。发现 DMSO 能诱导精原细胞中的 H 突变。这一异常结果可能归因于该化合物的病毒诱导特性。常用于治疗人类尿路感染的呋喃妥因对成熟精子细胞表现出非常阶段特异性的作用。从其敏感性和经济性方面讨论了 H 测试在致突变性测试中的价值。疑似 H 突变体的自发频率非常高，并且诱变剂和 DMSO 易于诱导突变频率增加，这表明 H 测试中发现的大多数组织不相容性可能是由于内源性病毒诱导的抗原性基因产物所致。然而，这并不妨碍 H 测试在致突变性测试中的适用性，反而似乎增强了其对烷基化诱变剂以及可能导致移码突变的诱变剂的敏感性。使用小鼠生殖细胞进行的其他突变和/或遗传性肿瘤易感性测试可以很容易地与 H 测试结合，因为测试动物不必处死，从而降低了测试成本。
