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A Comparison of Genotoxic Activity in Somatic Tissue and in Germ Cells of Drosophila Melanogaster

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Mutation, Cancer, and Malformation

Part of the book series: Environmental Science Research ((ESRH,volume 31))

Summary

Studies on the mutagenicity in germ line assays of representatives from practically all classes of procarcinogens/promutagens, altogether about 80 chemicals, indicated that Drosophila melanogaster has the enzymatic potential for converting a wide array of procarcinogens into genetically active species. Biochemical analysis of the enzymes involved in their biotransformation proved the presence and the inducibility in Drosophila of several types of cytochrome P-450 and of other components of the xenobiotics-metabolizing enzymes, such as aryl hydrocarbon hydroxylase (AHH) activity.

The considerable AHH-activity present in microsoma 1 preparations stands in marked contrast to the low mutagenic effectiveness generally observed when testing carcinogenic aroamtic amines and polycyclic hydrocarbons in the recessive lethal assay. Thus one crucial question concerning the action of these large two classe of procarcinogens is how their genetic effectivenes in Drosophila can be enhanced. Since it is not a a priori possible to conclude that gonadal tissue will always be the proper target for chemicals requiring metabolic activation, somatic mutation assays may provide a useful alternative for testing purposes, as opposed to germ cell assays.

In an attempt to study the usefulness of this approach, we compared the genotoxic effectiveness of a number of model mutagens in male and female germ cells with their activity in somatic tissue of females (white/whiteCO test) by treating first-instar larvae. By using the same protocol, MMS, bleomycin, 9,10-dimethylanthracene and 7,12-dimethylbenz (a) anthracene were quite efficient inproducing somatic recombination and mutations in female larvae, as opposed to only marginal effects in male and/or female germ cells. These findings raise the possibility that a high proportion of mutations were induced in premeiotic cells, and that those carrying a lethal mutation were eliminated by germinal selection. Calibration studies with 17 additional reference mutagens also suport the conclusion that somatic mutation assays might be particularly valuable as a complement to recessive lethal tests on heritable genetic damage.

The broad spectrum of heritable and somatic genetic alterations which can be determined in Drosophila suggests a model function for this system which may prove to be of increasing value in the future. By determining the mutagenic profile of a given genotoxic reagent as completely as possible, employing the nine parameters currently available for such an integrated analysis in Drosophila, it should be feasible to link certain types of DNA alkylation adducts with various genetic end points, as has already been demonstrated for a series of monofunctional alkylating agents, and for hexamethylphosphoramide (HMPA). Thus, analysis of multiple genetic parameters in Drosophila provides a means of gaining insight into the relationship between chemical interaction pattern and mutagenic mechanism.

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Authors and Affiliations

  1. Department of Radiation Genetics and Chemical Mutagenesis, Sylvius Laboratories, State University of Leiden, Wassenaarseweg 72, 2333 AL, Leiden, The Netherlands

    Ekkehart W. Vogel

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  1. Ekkehart W. Vogel
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Editors and Affiliations

  1. University of Michigan Medical School, Ann Harbor, Michigan, USA

    Ernest H. Y. Chu

  2. Oak Ridge National Laboratory, Oak Ridge, Tennesse, USA

    Walderico M. Generoso

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© 1984 Plenum Press, New York

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Vogel, E.W. (1984). A Comparison of Genotoxic Activity in Somatic Tissue and in Germ Cells of Drosophila Melanogaster . In: Chu, E.H.Y., Generoso, W.M. (eds) Mutation, Cancer, and Malformation. Environmental Science Research, vol 31. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2399-0_12

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  • DOI: https://doi.org/10.1007/978-1-4613-2399-0_12

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