Green S, Auletta A, Fabricant J, Kapp R, Manandhar M, Sheu C J, Springer J, Whitfield B
Mutat Res. 1985 Jul;154(1):49-67. doi: 10.1016/0165-1110(85)90009-0.
The term dominant lethal may be defined as death of the heterozygote arising through multiple chromosomal breaks. The assay is generally conducted by treating male animals, usually mice or rats, acutely (1 dose), subacutely (5 doses), or over the entire period of spermatogenesis. Animals treated acutely or subacutely are mated at weekly intervals to females for a sufficient number of weeks to cover the period of spermatogenesis. Those treated for the entire spermatogenic cycle are mated for 1 or 2 successive weeks at the termination of treatment. Females usually are killed at 14 days of pregnancy and examined for the number of total implantations in the uterus, the number of implantations classified as early deaths, and, in some cases, the number of corpora lutea. The category of early death is the most significant index of dominant lethality. A total of 249 papers were reviewed and 140 chemicals were evaluated. Of the 140 chemicals, 65 were positive by the criteria used by the Work Group in evaluating each publication. The category of "positive" includes those responses of a borderline nature. 99 chemicals were declared negative. There is considerable overlap of chemicals in both categories, which accounts for the incongruity in the total number of chemicals tested and the number considered positive and negative. A total of 44 animal carcinogens have been tested in the dominant lethal assay, 26 of which were positive and 18 negative for a correlation of 59%. The role of the assay should be that of confirming positive results from lower tier chromosomal aberration-detecting systems (confirming in the sense of indicating the ability of the chemical to penetrate gonadal tissue and to produce cytogenetic damage). The dominant lethal assay should not be used as a risk assessment method.
显性致死这一术语可定义为因多条染色体断裂导致杂合子死亡。该试验通常通过对雄性动物（通常是小鼠或大鼠）进行急性（1剂）、亚急性（5剂）处理，或在整个精子发生期进行处理来进行。经急性或亚急性处理的动物每周与雌性交配，持续足够多的周数以涵盖精子发生期。在整个精子发生周期接受处理的动物在处理结束后连续交配1或2周。雌性动物通常在怀孕14天时处死，并检查子宫内的总着床数、归类为早期死亡的着床数，在某些情况下，还检查黄体数。早期死亡类别是显性致死最显著的指标。共审查了249篇论文，评估了140种化学物质。在这140种化学物质中，按照工作组评估每份出版物所采用的标准，有65种呈阳性。“阳性”类别包括那些临界性质的反应。99种化学物质被判定为阴性。两类化学物质有相当多的重叠，这解释了所测试化学物质总数与被认为阳性和阴性的化学物质数量之间的不一致。共有44种动物致癌物在显性致死试验中进行了测试，其中26种呈阳性，18种呈阴性，相关性为59%。该试验的作用应该是确认来自较低层级染色体畸变检测系统的阳性结果（从表明化学物质穿透性腺组织并产生细胞遗传学损伤的能力的意义上进行确认）。显性致死试验不应用作风险评估方法。
