Biomedical subjects

E von Halle

Publications and source records attributed to E von Halle.

3 recordsLinked to original sources

PubMed1981

The mouse specific-locus test with agents other than radiations: interpretation of data and recommendations for future work.

The mouse specific-locus test with visible markers (SLT) has been the only extensively used method for detecting and quantifying the induction of heritable point mutations (intragenic changes and small deficiencies) in mammals. Mutations are detected in first-generation offspring; and scoring is simple, objective, and rapid. Different germ-cell stages can be sampled, including those of greatest pertinence for genetic risk assessment. The differential probability of involving the various loci of the marked set makes the method capable of detecting qualitative (as well as quantitative) differences between the actions of mutagens. Control SLT frequencies for males reported by 4 sets of investigators are in excellent agreement and were summed as a "historical control" (801406 observations) for use in our calculations. Experimental results were classified as positive, negative, or inconclusive based upon a multiple-decision procedure produced by the testing of the following 2 hypotheses: (1) the mutation frequency (induced + spontaneous) of treated mice is not higher than the spontaneous mutation frequency, and (2) the induced mutation frequency of treated mice is no less than 4 times the historical-control mutation frequency. Each hypothesis was tested at the 5% significance level. Because of the low mutation frequency in a very large control, the SLT is capable of yielding positive results in relatively small samples. We reviewed 58 publications, SLT results have been reported for 25 chemical agents, of which 17 (representing 21 chemical classes) gave results that were positive or negative by our criteria. The frequency of positive agents was 6 of 14, 5 of 5, and 0 of 1 conclusively tested, respectively, in spermatogonia, post-spermatogonial stages, and unspecified male germ cells. Depending on the chemical used, post-spermatogonial stages can be of greater, less, or equal sensitivity relative to spermatogonia. The SLT was strongly positive for some chemicals that are not mutagenic (or only weakly so) in lower systems, and there are several examples of the reverse situation. Factors which presumably operated to cause these differences (e.g., metabolism, transport, repair in germ cells) are likely also to operate for transmitted point mutations in man.

Animals↗

PubMed1981

Use of the mouse spot test in chemical mutagenesis: interpretation of past data and recommendations for future work.

The mouse spot test, developed 23 years ago, is an in vivo assay capable of detecting genetic effects of several kinds, including intragenic mutations, minute deficiencies, deletions (through breakage or nondisjunction) of various amounts of chromosomal material, and somatic crossing-over. The method involves exposing embryos that are heterozygous for a number of coat-color markers to the test agent, and, 3 weeks later, looking for clones of mutant cells, i.e., spots of color expressing the recessive marker in an otherwise black fur. Spots having other causes may also be induced, specifically white midventral spots due to cytotoxic effects, and certain spots resulting from misdifferentiation. Spot-test results have, to date, been reported from 7 laboratories. Because the control results for any one cross and solvent were found to be reasonably consistent between the laboratories, we pooled these to develop a "historical" control with which experimental results for the same cross and solvent were compared. Experimental results were classified as positive, negative, or inconclusive on the basis of a multiple-decision procedure produced by the testing of the following 2 hypotheses: (1) the mutation frequency (induced + spontaneous) in treated mice is not higher than the mutation frequency in the appropriate pooled control, and (2) the induced mutation frequency of the treated mice is no less than 4 times as high as the observed mutation frequency in the appropriate pooled control. Each hypothesis was tested at the 5% significance level. To date, 30 substances have been employed in the spot test, including 3 that are solvents for some of the others. Of the remaining 27 (26 compounds and 1 mixture), 16 were positive, 6 negative, and 5 inconclusive. The 26 compounds fell into 27 chemical classifications (using a system provided for use by the GENE-TOX program). The inadequacies in the design and reporting of some past experiments indicate a need for a carefully specified protocol. When properly done, the spot test will fulfill a useful role in mutagenicity testing programs because (1) it is an in vivo mammalian assay, (2) it detects genetic effects of many kinds, and (3) it is relatively rapid. Since the test appears well suited to the identification of potent mutagens, its main value should be in screening large numbers of substances and singling out the potentially worst offenders to be further studied in germ-line mutagenesis tests.

Animals↗

PubMed1980

Heritable translocation test in mice.

The status of the heritable-translocation test in mice with respect to its usefulness in practical testing was evaluated by using information available in the open literature. A total of 47 reports were evaluated; 29 were judged to contain adequate information to classify whether or not a given chemical induced heritable translocations. Heritable-translocation data were available for 32 compounds; data were not adequate for 15 compounds. Of the remaining 17 compounds, clear-cut determination of positive or negative effects was made for 14 compounds, while data for 3 compounds were only suggestive of either negative or positive effects. 10 chemicals have been shown to induce heritable translocations. These chemicals are either direct or indirect alkylating agents. The heritable-translocation test needs to be improved before it can be used in wide-scale practical testing. The most important question is whether or not historical controls can be used in tests for significance; the cost of concurrent controls is prohibitive. There is a need to standardize methods used in testing laboratories with respect to the size of error involved in classifying translocation heterozygotes and the power of the test. There is also a need to study in the effectiveness of non-alkylating clastogens in inducing heritable translocations in mice.

Animals↗