Germ cell testing

In vivo mammalian mutation tests are not restricted to germ cell tests. The mouse spot test described below is, again, a test used first for studying radiation-induced mutation but has also been used for screening chemicals for in vivo mutagenic potential. This test has had several proponents but compared with in vivo chromosomal assays is not widely used. 

Adler ID, Shelby MD, Boorman J, et al. (1994) Summary report of the working group on mammalian germ cell tests. Mutation Research 312 313-318. 

Where germ cell testing is required, judgment should be used to select the most appropriate test strategy. There are a number of tests available, which fall into two classes (1) tests in germ cells per se ( class 1 ) and (2) tests to detect effects in the offspring (or potential offspring) of exposed animals ( class 2 ). Three... 

Mouse visible or eleetrophoretie specifie-locus tests Assays for skeletal and cataract mutations Cytogenetic analy.sis and heritable translocation assays DNA damage and repair in rodent germ cells Dominant lethal assay... 

No A No A t (no CaM) Testes (germ cells), widespread HC03 sensor defect associated with absorptive hypercalciuria... 

Waters MD, Stack HF, Jackson MA, et al. 1994. The performance of short-term tests in identifying potential germ cell mutagens A qualitative and quantitative analysis. Mutat Res 341 109-131. 

The somatic cell gene replacement described above would obviously not be passed on to offspring. Other strategies to alter germ cell lines have been devised but have been tested only in experimental animals. A certain... 

A wheat germ, cell-free, translation extract was fractionated into three concentrated parts using ammonium sulfate the 0 - 40 % saturated fraction, the 40 - 60 % saturated fraction, and the ribosome fraction. These fractions were tested for their ability to enhance the translational activity of the wheat germ, cell-free extract for dihydrofolate reductase. The fortified cell-free system supplemented with the 0 - 40 % ammonium sulfate fraction enhanced the efficiency of protein synthesis by 50 %. 

Shima, A. and A. Shimada. 1991. Development of a possible nonmammalian test system for radiation-induced germ-cell mutagenesis using a fish, the Japanese medaka (Oryzias latipes). Proc. Natl. Acad. Sci. U.S.A. 88 2545-2549. 

With regard to the design of the test, mice are mated when 7-8 weeks old. By this age all germ cell stages are present. The test compound is normally administered by the IP route to maximize the likelihood of germ cell exposure. The preferred dose is just below the toxic level so long as fertility is not compromised. One lower dose should also be included. 

The spermatogonial test is used to identify substances that cause structural chromosome aberrations in mammalian spermatogonial cells, and is designed to investigate whether somatic cell mutagens are also active in germ cells. This test is not designed to measure numerical aberrations and is not routinely used for this purpose. 

The test is used to detect dominant lethal mutations. A dominant lethal mutation is one occurring in a germ cell, which does not cause dysfunction of the gamete but which is lethal to the fertihzed egg or developing embryo. 

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