Abstract
The introduction of foreign cells (e.g. ascites tumor cells) into laboratory mammals and their subsequent recovery after treatment of the host with exogenous chemicals to determine the induction of genetic effects (e.g. chromosomal aberrations) is a technique which has been employed for more than 20 years. The use of bacteria as indicators of induced point mutations was first described by Legator et al. (1969). In their technique which they called a host-mediated assay, the microbes (e.g. Salmonella typhimurium) were injected into the peritoneal cavity of mice and, thus, exposed to potentially mutagenic metabolites of the compound under test. Today a wide variety of genetical changes can be detected in several indicator organisms. In addition to the histidine-requiring strains of Salmonella which allow the detection of different types of back-mutations, some other enterobacteria have proven useful. Auxotrophic strains of Serratia marcescens to detect back mutations, and Escherichia coli bacteria in which both forward and back mutations can be assayed simultaneously in several different genes. With fungi or fungal spores as indicators further effects of genetical importance can be determined, e.g. the consequences of recombination processes such as mitotic gene conversion and mitotic recombination in the yeasts, and of deletions in Neurospora crassa (conidia). After the successful development of methods to measure the induction of point mutations in cultured mammalian cells, it is also possible now to use established animal cell lines (e.g. mouse lymphoma cells) in a host-mediated assay provided isogenic or compatible hosts are available.
During the past several years the route of administration of the indicator cells and the distribution of these cells within the animal body have been studied. Efforts have been made to bring the indicators into close contact with the reproductive organs or within the liver because this is the organ where most foreign compound metabolism is known to occur. Depending on the inoculation technique (in situ, intraperitoneal, intravenous) it is now possible to recover indicators out of testes, liver spleen, lungs and peritoneal cavity of treated animals in quantities large enough to perform genetic tests. A further improvement is the introduction of indicators within the intestinal tract of rodents; the first experiments along this line using Salmonella seem promising and have opened the way toward using common representatives of the intestinal flora such as Escherichia coli. In general it appears that the host-mediated assay technique is a useful tool to use in assessing the degree of mutagenicity and the organospecificity of foreign chemicals in living mammals and that it should be used until techniques that allow the detection of genetic events in the cells of the different organs have been developed. In the near future, host-mediated assays will have to be used to assess more quantitatively the mutagenicity of the numerous chemicals that have been found genetically active by using direct microsomal assays.
Further improvements of host-mediated assays are necessary. For instance, there is as yet no practical method for retention of microbial indicators long enough within the blood stream of living animals to perform genetic tests. This would be desirable for pharmaceutical reasons, e.g. for determination of the kinetics of appearance and removal of mutagenic factors within the blood stream. Preliminary experiments indicate that bacteriophages might be useful indicators, since they are present in blood in quantities sufficient for genetic analysis more than 24 h after intravenous injection. In contrast to all other indicators used so far, bacteriophages do not show any metabolism outside their bacterial hosts that might interfere with the mammalian metabolism. Studies are presently under way to determine what types of mutations or of genetic alterations are best detected after extracellular phage treatment.
Zusammenfassung
Das Einbringen von Fremdzellen (z. B. Ascites Tumorzellen) in Laborsäuger, um sie nach Behandlung der Wirtstiere und anschließender Wiedergewinnung auf genetische Effekte (z. B. Chromosomenaberrationen) zu untersuchen, ist eine Technik, die seit mehr als 20 Jahren durchgeführt wird. Die Verwendung von Bakterien als Indikatoren für den Nachweis von Punktmutationen wurde von Legator et al. (1969) erstmals beschrieben. Diese intraanimale Mutagenitätsprüfung („host-mediated assay“), bei der die Keime (Salmonella typhimurium) in die Leibeshöhle von Mäusen injiziert wurden, ist inzwischen in mancher Hinsicht weiterentwickelt worden.
Heute kann eine Vielzahl von genetischen Veränderungen mit verschiedenen Indikatororganismen untersucht werden. Zusätzlich zu den Rückmutationen erfassenden, Histidin-auxotrophen Salmonellen haben sich weitere Enterobakterien als brauchbar erwiesen. Neben Stämmen von Serratia marcescens werden Escherichia coli-Bakterien verwendet, in denen das Spektrum der erfaßten Mutationstypen auf Vorwärtsmutationen in mehreren Genen erweitert wurde. Mit Pilzen als Indikatoren können ferner zusätzliche Effekte von genetischer Bedeutung untersucht werden: Rekombinative Prozesse wie mitotische Genkonversion und mitotische Rekombination bei der Hefe Saccharomyces cerevisiae sowie Deletionen und rezessive Letalmutationen bei Neurospora crassa (Konidien). Seit der Entwicklung von Systemen, die es erlauben, auch Punktmutationen in Säugerzellkulturen zu erfassen, ist es möglich, etablierte tierische Zellen (z. B. Lymphoma-Zellen der Maus) in isogenen oder kompatiblen Tieren zu verwenden.
In den letzten Jahren wurde die Art der Verabreichung der Indikatorkeime und deren Verteilung innerhalb des Wirtstieres vielfältig variiert. Die Bemühungen gingen dahin, die Indikatorkeime näher an die Reproduktionsorgane zu bringen oder in unmittelbarer Nähe des Organs, in dem die meisten metabolischen Umwandlungen von Fremdstoffen geschehen, nämlich der Leber. Je nach Inokulationsweise (in situ, intraperitoneal, intravenös) ist es inzwischen möglich, genügend Keime für Mutagenitätsprüfungen aus Hoden, Leber, Milz, Lunge und Peritoneum behandelter Säuger zu erhalten. Um die organotrope Wirkung von mutagenen Substanzen umfassender zu untersuchen, wäre es weiterhin wichtig, das Vorhandensein mutagener Faktoren im Darmtrakt zu ermitteln. Erste Experimente deuten an, daß Salmonellen als brauchbare Indikatoren in Frage kommen und ermöglichen die Verwendung von Vertreter der üblichen Darmflora, z. B. Escherichia. Insgesamt kann festgestellt werden, daß sich die Methodik des host-mediated assay bewährt hat, um das Ausmaß der Mutagenität und der organspezifischen Wirkung von Fremdstoffen zu bestimmen und weiter Verwendung finden wird, bis Methoden zum direkten Nachweis von genetischen Veränderungen in Zellen der betreffenden Organe ausgearbeitet sind. Zunächst ist noch im host-mediated assay die Mehrzahl der Substanzen zu prüfen, die sich als aktiv in direkten mikrosomalen Tests erwiesen haben.
Weiterentwicklungen des host-mediated assay sind nötig: Bisher gibt es keine brauchbare Methode, um die Indikatorkeime bei solchen Mutagenitätsprüfungen lange genug in der Blutbahn der Wirtstiere zu halten. Dies wäre aus pharmakologischer Sicht wünschenswert, um u. a. den zeitlichen Verlauf des Auftretens und des Ausscheidens mutagener Produkte im Blut zu verfolgen. Erste Experimente mit Bakteriophagen deuten an, daß diese sich als Indikatoren eignen, da sie nach mehr als 24 h noch in genügender Anzahl in der Blutbahn vorhanden sind. Im Gegensatz zu den anderen Indikatoren haben Bakteriophagen keinen Eigenstoffwechsel, der mit dem des Wirtstieres interferieren könnte. Zur Zeit wird untersucht, welche Systeme zur Bestimmung von induzierten Mutationen oder anderen genetischen Effekten in extrazellulären Phagen hierbei geeignet sind.
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References
Adler, I. D.: Cytogenetic analysis of ascites tumor cells of mice in mutation research. In: Chemical mutagenesis in mammals and man (F. Vogel, G. Röhrborn, Eds.), PP-251–259. Berlin-Heidelberg-New York: Springer 1970
Ames, B. N., Lee, F. D., Durston, W. E.: An improved bacterial test system for the detection and classification of mutagens and carcinogens. Proc. nat. Acad. Sci. (Wash.) 70, 782–786 (1973)
Ames, B. N., McCann, J., Yamasaki, E.: Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test. Mutation Res. 31, 347–364 (1975)
Arrighi, F. E., Hsu, T. C., Bergsagel, D. E.: Chromosome damage in murine and human cells following cytoxan therapy. Tex. Rep. Biol. Med. 20, 545–549 (1962)
Bidwell, K., Weber, E., Nienhold, I., Conner, T., Legator, M. S.: Comprehensive evaluation for mutagenic activity of dieldrin. Mutation Res. 31, 314 (1975)
Boyland, E., Clegg, J. W., Koller, P. C., Rhoden, E., Warwick, O. H.: Brit. J. Cancer 2, 17 (1948)
Braun, R., Schöneich, J.: The influence of ethanol and carbon tetrachloride on the mutagenic effectivity of cyclophosphamide in the host-mediated assay with Salmonella typhimurium. Mutation Res. 31, 191–194 (1975)
Brewen, J. G.: Host-mediated cytogenetic assay. Mutation Res. 31, 5–8 (1975)
Brewen, J. G., Nettesheim, P., Jones, K. P.: A host-mediated assay for cytogenetic mutagenesis: Preliminary data on the effect of methyl methanesulfonate. Mutation Res. 10, 645–649 (1970)
Bronzetti, G., Barale, R., Baroncelli, S., Cammellini, A., Corsi, C., Leporini, C., Loprieno, N., Nieri, R., Nozzolini, M., Rossi, A. M.: Utilizzazione dell'host mediated assay nella valutazione della genotossicita' dei mutageni chimici. Associazione Genetica Italiana XX, 6–8 (1975)
Brusick, D., Legator, M. S.: Utilization of Saccharomyces cerevisiae in the host-mediated assay. EMS Newsletter 4, 31–32 (1971)
Brusick, D., Mayer, V. W.: New developments in mutagenicity screening techniques with yeast. Env. Hlth Perspect., Exp. Issue 6, 83–96 (1973)
Buckton, K. E., Nettesheim, P.: In vitro and in vivo culture of mouse peripheral blood for chromosome perparations. Proc. Soc. exp. Biol. (N.Y.) 128, 1106–1110 (1968)
Buselmaier, W., Röhrborn, G., Propping, P.: Mutagenitäts-Untersuchungen mit Pestiziden im Hostmediated assay und mit dem Dominanten Letaltest an der Maus. Biol. Zbl. 91, 311–325 (1972)
Capizzi, R. L., Smith, W. J., Field, R., Papirmeister, B.: A host-mediated assay for chemical mutagens using the L5178Y:Asn-murine leukemia. Mutation Res. 21, 6 (1973a)
Capizzi, R. L., Summers, W. P., Papirmeister, B.: Use of the asparagine auxotroph of the L5178Y murine leukemia for the detection of chemical mutagens in vitro and in the host-mediated assay. Env. Hlth Perspect., Exp. Issue 6, 137–143 (1973b)
Chu, E. H. Y.: Induction of chromosome aberrations with alkylating agents in Ehrlich ascites tumor cells in vivo: A host-mediated assay for chemical mutagens. Genetics 64, 12–13 (1970)
Chu, E. H. Y., Malling, H.: Induction of mutations in mammalian cells implanted in heterologous hosts. Env. Mutagen Soc. Newsletter 6, 8–9 (1972)
Dean, B. J., Doak, S. M. A., Funnell, J.: Genetic studies with dichlorvos in the host-mediated assay in liquid medium using Saccharomyces cerevisiae. Arch. Toxikol. 30, 61–66 (1972)
de Serres, F. J., Malling, H. V.: Measurement of recessive lethal damage over the entire genome and at two specific loci in the ad-3 region of a two-component heterokaryon of Neurospora crassa. In: Chemical mutagens (A. Hollaender, Ed.), pp. 311–342. New York: Plenum Press 1971
Ellenberger, J., Mohn, G.: More about intrasanguineous mutagenicity testing. Mutation Res. 29, 235–236 (1975)
Fahrig, R.: Metabolic activation of aryldialkyltriazenes in the mouse: Induction of mitotic gene conversion in Saccharomyces cerevisiae in the host-mediated assay. Mutation Res. 13, 436–439 (1971)
Fahrig, R.: Experiments with the host-mediated assay utilizing induction of mitotic gene conversion in Saccharomyces cerevisiae. Mutation Res. 21, 30 (1973b)
Fahrig, R.: Development of host-mediated mutagenicity tests. I. Differential response of yeast cells injected into testes of rats and peritoneum of mice and rats to mutagens. Mutation Res. 26, 29–36 (1974)
Fahrig, R.: Development of host-mediated mutagenicity tests-yeast systems. II. Recovery of yeast cells out of testes, liver, lung, and peritoneum of rats. Mutation Res. 31, 381–394 (1975)
Fahrig, R., Grafe, A., Buselmaier, W.: Über die mutagene Wirkung des Methylmethansulfonats (MMS) in vitro und im „Host-mediated Assay. Arch. Toxicol. 34, 9–15 (1975)
Farrow, M. G.: The use of trimethylphosphate (TMP) as a control agent in the dominant lethal, cytogenetic and host-mediated assays. Mutation Res. 31, 314 (1975)
Ficsor, G., Beyer, R. D., Janca, F. C., Zimmer, D. M.: An organ-secific host-mediated microbial assay for detecting chemical mutagens in vivo: Demonstration of mutagenic action in rat testes following streptozotocin treatment. Mutation Res. 13, 283–287 (1971)
Fischer, G. A.: The host-mediated mammalian cell assay. Agents and Actions 3, 93–98 (1973)
Fischer, G. A., Lee, S. Y., Calabresi, P.: Detection of chemical mutagens using a host-mediated assay (L5178Y) mutagenesis system. Mutation Res. 26, 501–511 (1974)
Frohberg, H., Bauer, A.: Mutagenicity trials under toxicological aspects. Arzneimittel-Forsch. 36, 380–386 (1973)
Gabridge, M. G., Legator, M. S.: A host-mediated microbial assay for the detection of mutagenic compounds. Proc. Soc. exp. Biol. (N.Y.) 130, 831–834 (1969)
Gabridge, M. G., Oswald, E. J., Legator, M. S.: The role of selection in the host-mediated assay for mutagenicity. Mutation Res. 7, 117–119 (1969)
Gingold, J. L., DiPasquale, G.: Serum analysis in rats following the administration of endotoxin. Toxicol. appl. Pharmacol. 36, 603–606 (1976)
Gorodischer, R., Krasner, J., McDewitt, J. J., Nolan, J. P., Yaffe, S. J.: Hepatic microsomal drug metabolism after administration of endotoxin in rats. Biochem. Pharmacol. 25, 351–353 (1976)
Grafe, A., Lorenz, R., Vollmar, J.: Testing the mutagenic potency of chemical substances in a linear host-mediated assay. I. Experimental microbiological basis. Mutation Res. 31, 205–216 (1975)
Green, M. H. L., Muriel, W. J.: Mutagen testing using trp + reversions in Escherichia coli. Mutation Res. 38, 3–32 (1976)
Hauser, R., Matter, B. E.: Localization of E. coli K-12 in livers of mice used for an intrasanguineous hostmediated assay. Mutation Res. 46, 45–48 (1977)
Huang, C. C.: A modified host-mediated assay using human cells. 7th Meeting. Env. Mutagen Soc., Abstr. Booklet, 31–32 (1976)
Igali, S., Gazso, L. G.: Mutagenic effect of the alkylating cytostatic drug degranol tested in hostmediated assay with E. coli WP2 strain. Mutation Res. 21, 190 (1973)
Jarolmen, H., Bondi, A., Crowell, R. L.: Transduction of Staphylococcus aureus to tetracycline resistance in vivo. J. Bact. 89, 1286–1290 (1965)
Kada, T., Tutikawa, K., Sadaie, Y.: In vitro and host-mediated “rec-assay” procedures for screening chemical mutagens; and phloxine, a mutagenic red dye detected. Mutation Res. 16, 165–174 (1972)
Kehler, E., Röhrborn, G., Propping, P., Buselmaier, W.: Zur Mutagenität des INH. Pneumonologie 148, 223–226 (1973)
Kolar, G. F., Fahrig, R., Vogel, E.: Structure-activity dependence in some novel ring-substituted 3,3-dimethyl-1-phenyl-triazenes. Genetic effects in Drosophila melanogaster and in Saccharomyces cerevisiae by a direct and a host-mediated assay. Chem.-Biol. Interactions 9, 365–378 (1974)
Koller, P. C.: Dicentric chromosomes in a rat tumor induced by an aromatic nitrogen mustard. Heredity 6, 181–196 (1953)
Koller, P. C., Casarini, A.: Comparison of cytological effects induced by X-rays and nitrogen mustard. Brit. J. Cancer 6, 173–185 (1952)
Krafft, S., Onken, A.: Induction of mitotic gene conversion in Saccharomyces cerevisiae with chlordiazepoxide and its n-nitroso derivative in a host-mediated assay. Mutation Res. 34, 333–336 (1976)
Lee, S. Y.: Current status of the host-mediated L5178Y system for detecting chemical mutagens. Env. Hlth Perspect., Exp. Issue 6, 145–149 (1973)
Legator, M. S.: The host-mediated assay, a practical procedure for evaluating potential mutagenic agents. In: Chemical mutagenesis in mammals and man (F. Vogel, G. Göhrborn, Eds.), pp. 260–270. Berlin-Heidelberg-New York: Springer 1970
Legator, M. S.: Procedure for conducting the host-mediated assay utilizing bacteria (“Salmonella typhimurium”). Agents and Actions 3, 111–115 (1973)
Legator, M. S., Malling, H. V.: The host-mediated assay, a practical procedure for evaluating potential mutagenic agents in mammals. In: Chemical mutagens (A. Hollaender, Ed.), pp. 569–589. New York: Plenum 1971
Loprieno, N., Barale, R., Bauer, C., Baroncelli, S., Bronzetti, G., Cammellini, A., Cinci, A., Corsi, G., Leporini, C., Nieri, R., Nozzolini, M., Serra, C.: The use of different test systems with yeasts for the evaluation of chemically induced gene conversions and gene mutations. Mutation Res. 25, 197–217 (1974)
Malling, H. V.: ad-3 Mutations induced in Neurospora conidia during their stay in the peritoneal cavity of mice and rats. Genetics 64, 40–41 (1970)
Malling, H. V.: Mutagenic activation of carcinogens in vitro and in the host-mediated assay. Genetics 68 (Suppl.), 41–42 (1971)
Malling, H. V.: Mutation induction in Neurospora crassa incubated in mice and rats. Molec. gen. Genet. 116, 211–222 (1972)
Malling, H. V.: Host-mediated assay, pro and con. In: Molecular and environmental aspects of mutagenesis. (L. Prakash et al., Eds.), pp. 159–177. Springfield: Thomas 1974a
Malling, H. V.: Mutagenic activation of dimethylnitrosamine and diethylnitrosamine in the host-mediated assay and the microsomal system. Mutation Res. 26, 465–472 (1974b)
Malling, H. V., Cosgrove, G. E.: The internal level of mutagens in mammals. In: Chemical mutagenesis in mammals and man (F. Vogel, G. Röhrborn, Eds.), pp. 271–278. Heidelberg-Berlin-New York: Springer 1970
Malling, H. V., Frantz, C. N.: In vitro versus in vivo metabolic activation of mutagens. Env. Hlth Perpect., Exp. Issue 6, 71–82 (1973)
Martone, W. J., Mukai, F. H.: Bacteriophage T4 as an indicator organism for the host-mediated assay system. Proc. Amer. Ass. Cancer Res. 13, 113 (1972)
Mohn, G.: Intrasanguineous mutagenicity test with bacteria. Mutation Res. 21, 347 (1973)
Mohn, G., Ellenberger, J.: Mammalian blood-mediated mutagenicity tests using a multipurpose strain of Escherichia coli K-12. Mutation Res. 19, 257–260 (1973)
Mohn, G., Ellenberger, J., McGregor, D.: Development of mutagenicity tests using Escherichia coli K-12 as indicator organism. Mutation Res. 25, 187–196 (1974)
Mohn, G., Ellenberger, J., McGregor, D., Merker, H. J.: Mutagenicity studies in microorganisms in vitro, with extracts of mammalian organs, and with the host-mediated assay. Mutation Res. 29, 221–233 (1975)
Mohn, G. R., Maier, P., Bürki, K.: The use of bacteriophages as indicators in host-mediated assays. Longevity of phages, T4, λ, and κ in the bloodstream of mice. Mutation Res. 48, 367–370 (1977)
Moroson, H., Furlan, M.: Single strand breaks in DNA of Ehrlich ascites tumor cells produced by methyl hydrazine. Radiat. Res. 40, 351–365 (1969)
Morrison, J.: Bacteriophage in the treatment and prevention of cholera. London: Lewis 1932
Münzner, R., Renner, H. W.: Mutagenität von bestrahltem Tierfutter im host-mediated assay mit Salmonella typhimurium G46. Int. J. Radiat. Biol. 27, 371–375 (1975)
Münzner, R., Renner, H. W.: Mutagenitätsprüfung von bestrahltem Versuchstierfutter im Host-mediated assay mit Salmonella typhimurium TA 1530. Zbl. Vet.-Med. B23, 117–121 (1976)
Nettesheim, P., Makinodan, T.: In vivo chamber culture technique. In: Methods in developmental biology (F. H. Wilt, N. K. Wessels, Eds.), pp. 471–483. New York: Crowell 1967
Osebold, J. W., Outteridge, P. M., Pearson, L. D.: Mutation of Listeria monocytogenes after prolonged in vivo survival in diffusion chambers. Infect. Immun, 1, 209–211 (1970)
Propping, P., Buselmaier, W.: The influence of metabolism on mutagenic activity in the host-mediated assay. Arch. Toxikol. 28, 129–134 (1971)
Propping, P., Röhrborn, G., Buselmaier, W.: Comparative investigations on the chemical induction of point mutations and dominant lethal mutations in mice. Molec. gen. Genet. 117, 197–209 (1972)
Propping, P., Röhrborn, G., Buselmaier, W.: Comparative investigations on the mutagenic activity of isoniazid in mammalian test systems. Mutation Res. 21, 44–45 (1973)
Ray, V. A., Holden, H. E., Ellis, J. H., Hyneck, M. L.: A study of triflipromazine in dominant-lethal, cytogenetic and host-mediated assay. Mutation Res. 18, 301–309 (1973)
Ray, V. A., Holden, H. E., Salsburg, D. S., Ellis, J. H., Just, L. J., Voyer, M. H.: Comparative studies of induced mutations with host-mediated, dominant lethal, and cytogenetic assays. Mutation Res. 21, 12 (1973a)
Ray, V. A., Holden, H. E., Ellis, J. H., Hyneck, M. L.: The mutagenic activity of 6-mercaptopurine in host-mediated and dominant lethal assays. Mutation Res. 21, 31 (1973b)
Ray, V. A., Holden, H. E., Salsburg, D. S., Ellis, J. H., Jr., Just, L. J., Hyneck, M. L.: Comparative studies of ethyl methane-sulfonate-induced mutations with host-mediated, dominant lethal, and cytogenetic assays. Toxicol. appl. Pharmacol. 30, 107–116 (1974)
Rieger, R., Michaelis, A., Schöneich, J., Fischer, G. W., Lohs, K. H.: Über die Induktion von Chromatidenaberrationen durch quartäre N-Acylvinyl-Stickstoffiost-Verbindungen. Studia biophysica 17, 205–212 (1969)
Röhrborn, G., Propping, P., Buselmaier, W.: Mutagenic activity of isoniazid and hydrazine in mammalian test systems. Mutation Res. 16, 189–194 (1972)
Rozmiarek, H., Capizzi, R. L., Papirmeister, B., Fuhrman, W. H., Smith, W. J.: Mutagenic activity in somatic and germ cells following chronic inhalation of sulfur mustard. Mutation Res. 21, 13–14 (1973)
Ryttman, H., Zetterberg, G.: Induction of mitotic recombination with n-methyl-n′-nitro-n-nitrosoguanidine (MNNG) in Saccharomyces cerevisiae. A comparison between treatment in vitro and in the host-mediated assay. Mutation Res. 34, 201–216 (1976)
Schöneich, J.: Zur Frage der mutagenen Wirkung von Äthylalkohol: Hum. Genet. 3, 84–85 (1966)
Schöneich, J., Braun, R.: Die Prüfung von Arzneimitteln auf Mutagenität. Der „host-mediated assay. Zbl. Pharm. 114, 689–698 (1975)
Siebert, D.: Comparison of the genetic activity of cyclophosphamide, ifosfamide and trofosfamide in host-mediated assays with the gene conversion system of yeast. Z. Krebsforsch. 81, 261–267 (1974)
Tutikawa, K., Kada, T.: Studies on the mutagenicity of furylfuramide: results of the host-mediated recassay and dominant lethal test in mice. Mutation Res. 31, 271 (1975)
Vogel, E., Fahrig, R., Obe, G.: Triazenes, a new group of indirect mutagens. Comparative investigations of the genetic effects of different aryldialkyltriazenes using Saccharomyces cerevisiae, the host-mediated assay, Drosophila melanogaster, and human chromosomes in vitro. Mutation Res. 21, 123–136 (1973)
Wheeler, L. A., Carter, J. H., Soderberg, F. B., Goldman, P.: Association of Salmonella mutants with germ free rats: Site specific model to detect carcinogens as mutagens. Proc. nat. Acad. Sci. (Wash.) 72, 4607–4611 (1975)
Zeiger, E.: Some factors affecting the host-mediated assay response. Env. Hlth Perspect., Exp. Issue 6, 101–109 (1973)
Zeiger, E., Brusick, D.: The host-mediated assay — a protocol for Salmonella and Saccharomyces. EMS Newsletter 5, 33 (1971)
Zeiger, E., Legator, M. S.: Mutagenicity of N-nitrosomorpholine in the host-mediated assay. Mutation Res. 12, 469–471 (1971)
Zeiger, E., Legator, M. S., Lijinsky, W.: Mutagenicity of N-nitrosopiperazines for Salmonella typhimurium in the host-mediated assay. Cancer Res. 32, 1598–1599 (1972)
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Mohn, G.R. Actual status of mutagenicity testing with the host-mediated assay. Arch. Toxicol. 38, 109–133 (1977). https://doi.org/10.1007/BF00293669
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DOI: https://doi.org/10.1007/BF00293669