Document daO2RngOBb4oG0vbMYQ5B7nKR

m* ` tOwil. Camcjut VW. fra, Kk4-, Apul 14*)*? p.24l literature Survey of Bacterial, Fungai, and Drosophila Assay Systems Used in the Evaluation of Selected Chemical Compounds for Mutagenic Activity'12 M. M. Brown,1 *4 *J. S. Wa**om, 3 H. V. Mailing, s M. D. Shelby, 6 and E. S. Von Halle - ` ABSTRACT--Uteratur* report* were surveyed, with reaulta noted from experiment* In aeven nonmammalian as*ay ayatama uaad tor the detection of mutagenicity or other related genetic (tecta. A comparison waa made of the acttvltlea of 54 aalected noncardnogena, procardnogena, and ultimate cardnogen* as revealed by these test system*. Ol the compound* teated, 49 (91%) were active In on* or more of the assays, and 42 (78%) were positive In at least one system without having to be melaboUcalty activated. In one or mom test systems, 17/17 (100%) ol the ultimate carcinogen*, 27/28 (96%) of the procardnogena, and 6/9 (67%) of the noncardnogena were positive. The Ames Sa/mon*//a-mlcro*ome assay responded with Increased mutation frequency to 37/44 (84%) of the carcinogenic compound* but to only 2/8 (25%) ot the noncardnogena tested. The Drosophila system responded to 19/21 (90%) of the carcinogens and to 3/6 (50%) of the noncarcinogens. Prophages ware Induced when lysogenic bacteria went exposed to 12/21 (57%) of the carcino gens, but not enough teat* were don* with the noncardnogena (1/3, or 33%) for a comparison. The other system* reviewed, such as the killing of rapalr-daflclent bactaria, mutations In Esche richia coif and Neurotpora crease, and the hoat-medlated assay, war* not challengad by anough of the compound* for valid comparisons.--J N*8 Cancer Inst 62: 541-671, 1979. | Results were summarized from published papers that Sported the use of selected nonmammalian assay systems to measure the mutagenic activity of chemical compounds of special interest to the National Cancer Institute. The chemicals considered in this summary are shown in table 1 and have been classified as either ultimate carcinogens, procarcinogens, or noncardnogens in table 5. Other compounds not appearing in this list are sometimes included in the text for com parison. The present compendium is limited to systems in which investigators used Neurospora crassa, Esche richia coli, Salmonella typhimurium. Drosophila melanogaster, or the induction of prophage or other episomes in various bacteria. Information was found for 54 of the 103 compounds listed in table 1. Results from these studies will be considered in sections by organism and are summarized in table 5. The use of nonmammalian assay systems for the detection of chemically induced mutations has been extensively reviewed by de Senes {1) and mentioned by many other investigators {2-9). The spedfic use of microbial assay systems in cancer research has been recently reviewed by Rosenkranz (20) and McCann et al. {11, 12). This paper attempts to collate published information on the evaluation of spedfic chemical compounds in nonmammalian systems for possible use in assessing the value of such systems in predicting potential cardnogenic activity. We call spedal atten tion to the fact that this is a literature summary and not a critical review. Wc have rot attempted to evaluate the interpretations of the data made by the authors of the cited papers. Furthermore, citation of results from all available literature or inclusion of results from papers in the most current literature was not feasible. We have, however, tried to be as compre hensive as possible. NEUROSPORA CRASSA N. ctassa has been used extensively in the evaluation of chemicals for mutagenic activity since Beadle and Abbreviations used: AF=2-fJuorcnaminc; AFBi= afJatoxin fit; AFBj wafiaioxin B?; AO = acridine orange; BA" bcn^ajanihraccne; fiPbcm[fl]pyrene; BPL^ jB-propiolacione; BrdUrd-5*bromo*2'dcoxyuridine; BrUra --5*bromouracil; DAB**4-(N,N-dimeihylaimno)axobenzene; DBA"dibcnz{fl,A)anihracene; DEB = l,2.'3,4*diepoxybutane; DNAsN*mtro$odiethylamine; DMBAe7,i2-dimethyIbenz(a]* anthracene; DMN-'N-nitrosodimethyUnaLnc; 2-FAA"N-2*fluorenyIacctamide; FdUrd*5*fluoro-2'-deoxyuridine; FUra* 5-fluorouracil; HA**hydroxylamine; HNj**ntirogtfl rotucard(i); 4HAQO4-(by* droxyamino^tiinoJine N*oxide; ldUrd*5-iodo2'-deoxyuridinc; MAMmcthylaioxymethanol; MCAS-mcthylcholamhrene; DAB *" 3'*methyl *4 *(dimethylamino)azobeTuene; MNNG * N-methylAP-niiro-N-nitrosoguanidinc; N-Ac02-FAA *= A^acetoxy-N-2-flu orenyUceumide; NEU = N-niiroso ethylurea; NFTT*=N-{4-{5-nitro-2* furyl)-2-ihiazolyl]formamide; NMU^N-nitroso methylurta; N-OH-2AF AAhydroxy-2-aminofluorcne; N-OH*2-FAA--N-hydroxy*N-(2fluorenyDacetamide; 4NQO**4-nitroquinoline N-oxide; l-OH-2FAA ]-hydroxy-A/*2-nuorcnylaccumide; PDMT*= l-phcnyl-53-<iimcthyltriaaenc; PMMT-- l-phcnyl-3-meihyltriaienc. 1 Received January 5, 1978; revised July 20, 1978; accepted August 8, 1978. a Supported by Public Health Service (PHS) contract 40-247-70 from the National Institute of Environmental Health Sciences, PHS contract 40-355-72 from die National Cancer Institute, and contract W-7405-cng-26 from the Department of Energy under contract with the Oak Ridge National Laboratory. 1 Environmental Mutagen Information Center (EMIC). Informa tion Center Complex/Information Division, Oak Ridge National Laboratory, P.O. Box Y, Bldg. 9224, Oak Ridge, Term. 37830. * Department of Biology, Knoxville College, Knoxville, Term. 37921, 1 Laboratory of Biochemical Genetics, P.O. Box 12233, National Institute of Environmental Health Sciences, Research Triangle Park, N.C 27709. 4 Office of the Associate Director (or Genetics, P.O. Box 12233. National Institute of Environmental Health Sciences. 1 Wc thank all EMIC staff members for their help, especially W. J. Barnard for typing the manuscript. We also thank those who reviewed this manuscript, especially Dr. Lionel A. Poirier. ,VOt_ ez, NO. 4. APRIL 1919 841 NATL CANCER INST J