bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of SOS genes of Escherichia coli by chromium compounds
Authors: Llagostera Montserrat , Garrido Salvador , Guerrero Ricardo , Barbé Jordi
Published: February 2007

The induction of several SOS genes of Escherichia coli such as recA, umuC, and sfiA by hexavalent (K2Cr2O7, K2CrO4, and CrO3) and trivalent (CrCl3, Cr(NO3)3, and (CH3COO)3Cr) compounds of chromium was studied. Induction was measured as β‐galactosidase activity, using lacZ gene fusions under the control region of different SOS genes. The hexavalent chromium forms induced the genes responsible for massive synthesis of RecA protein, error‐prone repair, and inhibition of cell division. On the other hand, the trivalent chromium compounds were unable to induce any of the SOS genes tested. Individual assay of hexavalent chromium compounds showed that K2Cr2O7 was a stronger inducing agent of those three SOS genes tested than K2CrO4, which, in turn, was stronger than CrO3. All this data led to the conclusion that hexavalent chromium compounds, but not trivalent, are proficient agents of induction of the SOS system and can produce indirect mutagenesis in Escherichia coli.
Induction of sister chromatid exchanges in murine colonic tissue
Authors: Couch David B. , Gingerich John D. , Stuart Earl , Heddle John A.
Published: February 2007

As cancers of the large bowel arise primarily in the epithelial cells of the colon, measurement of genetic damage induced in those cells may aid in elucidating contributing factors in the etiology of the disease. Accordingly, procedures for the in vivo measurement of sister chromatid exchanges (SCE) have been adapted for use with colonic cells. Agar‐coated 5‐bromo‐2′‐deoxyuridine (BrdUrd) tablets were implanted (s.c.) in mice and colonic tissue prepared for measurement of SCE 48 hr later. When mice were treated by intraperitoneal injection with 20 mg/kg 1,2‐dimethylhydrazine (DMH), a colon carcinogen, a significant increase over control SCE frequencies was found when treatment with carcinogen occurred in the interval from 14 hr before to 36 hr following BrdUrd administration. Treatment with DMH 2 hr following implantation of BrdUrd produced a dose‐dependent increase in SCE frequencies, with the highest dose (20 mg/kg) resulting in frequencies approximately twice those of controls. Dimethylhydrazine was not found to be effective in inducing SCE in bone marrow cells of mice. As SCE can be induced by carcinogens and mutagens, measurement of SCE in colonic epithelium may be useful in identifying potential colon carcinogens.
A review of the symposium on aneuploidy: Etiology and mechanisms
Authors: Hoffmann George R. , Dellarco Vicki L. , Voytek Peter E.
Published: February 2007

A symposium titled “Aneuploidy: Etiology and Mechanisms” was held in Washington, D.C., in March, 1985. The stimulus for convening it was the growing concern that environmental agents with the capacity to induce aneuploidy can have detrimental effects on human health. Major components of the symposium were devoted to an analysis of human aneuploidy, mechanisms by which aneuploidy originates, and tests for the detection of agents that induce aneuploidy. This review outlines the content of the symposium, its conclusions, and major uncertainties in the field.
Glutathione: A protective agent in Salmonella typhimurium and Escherichia coli as measured by mutagenicity and by growth delay assays
Authors: Owensm Roland A. , Hartman Philip E.
Published: February 2007

Cultures of some aerobically grown strains of Salmonella typhimurium and Escherichia coli contain up to 24 μM extracellular glutathione (GSH) [Owens RO, Hartman PE (1985): Environ Mutagen 7(Suppl 3): 47] in addition to having intracellular GSH concentrations in the millimolar range. The addition of 26 μM GSH to cultures of Salmonella typhimurium strain TA1534 partially protected the bacteria from the toxic effects causing growth delay by 54 μM N‐methyl‐N'‐nitro‐N‐nitrosoguanidine (MNNG). When MNNG was preincubated with equimolar GSH, the mutagenicity of the MNNG was neutralized. The addition of micromolar GSH to cultures of an Escherichia coli GSH− strain protected the cells from growth inhibition by micromolar concentrations of mercuric chloride, methyl mercuric chloride, silver nitrate, cisplatin, cadmium chloride, cadmium sulfate, and iodoacetamide. In the cases of mercuric chloride, cisplatin, MNNG, silver nitrate, and iodoacetamide, reaction products with GSH were detected by paper chromatography. In contrast to reduced GSH, micromolar concentrations of oxidized glutathione (GSSG) provided little or no protection and formed no detectable reaction products. Export of GSH by enteric bacteria may provide an important defense mechanism against exogenous toxic agents otherwise active in the micromolar range.
Genetic and physiological modulation of anthracycline‐induced mutagenesis in Salmonella typhimurium
Authors: Cebula Thomas A.
Published: February 2007

The genotoxic properties of adriamycin and daunomycin, anthracycline antibiotics effective in the treatment of a wide variety of malignancies, were examined in the Salmonella/Ames reverse‐mutation test. A novel time‐ and temperature‐dependent phenomenon that potentiates the mutagenicity of these compounds, termed mutational enhancement, is described. The results of congeneric and chemical attenuation studies imply that anthracycline‐induced free radicals contribute substantively to the mutagenic potentials of adriamycin and daunomycin. These studies show that adriamycin and daunomycin are not simple intercalative compounds. Rather, anthracycline‐induced mutagenesis entails at least two separate but intimately related steps, namely, intercalation within discrete base sequences and the free‐radical‐mediated events that ensue. Implications of the nonrandom and site‐specific action of the anthracyclines are discussed.
Comparison of in vivo and in vitro cytogenetic assay results
Authors: Thompson Edward D.
Published: February 2007

In vitro mutagenicity assays have largely replaced whole animal studies for screening compounds for genotoxic potential. While numerous comparisons have been made between the results of these assays and cancer assays in rodents, comparisons between in vitro and in vivo mutagenicity studies where the genetic endpoints are the same have not been published. To this extent, the published literature was reviewed for chemicals that had been tested in both in vitro and in vivo cytogenetic assays. Two hundred sixteen chemicals were identified, and definitive test results were obtained for 181 of them. Results from the two assays agreed on 126 of the compounds and of the 55 compounds for which the results did not agree, 53 were positive in vitro and negative in vivo. The proportion of “false positives” and the significance of the two “false negatives” are discussed.
Mutational specificity of animal cell DNA polymerases
Authors: Roberts John D. , Kunkel Thomas A.
Published: February 2007

Since DNA polymerases are involved in DNA replication, recombination, and repair, the frequency with which these enzymes commit errors during synthesis is likely to be an important factor in controlling mutation rates in cells. The fidelity of DNA polymerases was originally studied by following misincorporation using synthetic nucleic acid templates containing only one or two bases. Later, by assaying for reversion of an amber codon after copying φX174 single‐stranded DNA molecules, the base substitution accuracy of in vitro DNA synthesis on natural DNA was determined. Most recently, a forward mutation assay has been developed that uses gap‐filling synthesis on an M13mp2 DNA template, thus permitting the detection of a variety of different errors during DNA synthesis on natural DNA templates. Detailed mutational spectra for animal cell polymerases‐α, β, and γ have been determined and demonstrate that a variety of errors can be generated by these purified enzymes.

The frequencies of base mispairs, base additions, and deletion errors by DNA polymerases vary widely and depend on both the DNA sequence and the enzyme used. An understanding of the mechanisms by which DNA polymerases avoid or generate various mutations depends on the definition of the parameters that influence the frequency and specificity of particular errors. Future experiments will combine the use of the methods available to measure fidelity with advances in DNA replication enzymology and should lead to exciting new insights into the mechanisms of spontaneous mutagenesis.
Short‐term test results for NTP noncarcinogens: An alternate, more predictive battery
Authors: Ennever Fanny K. , Rosenkranz Herbert S.
Published: February 2007

A battery of short‐term tests used to predict whether or not a chemical is a carcinogen must be both sensitive (correctly identifying carcinogens) and specific (correctly identifying noncarcinogens). A recent publication [Shelby and Stasiewicz, 1984, Environ Mutagen 6:871–876] of results in four short‐term tests for 70 noncarcinogens tested under the aegis of the National Toxicology Program (NTP) indicates that the battery of short‐term tests lacked specificity. We have analyzed these results using the Carcinogen Prediction and Battery Selection (CPBS) procedure and calculated that the specificity of the NTP battery is indeed very low, i.e., 0.50. Using published data from NTP, the GeneTox program of EPA, and the collaborative study of the WHO International Programme on Chemical Safety, we have constructed an alternate battery that has fewer false positives; this battery has a specificity of 0.80. Thus, the lack of specificity of the original NTP battery does not imply that no set of short‐term tests is able to predict carcinogenicity accurately.
Inactivity of glycerol formal in a mouse micronucleus assay: Relationship to its teratogenicity
Authors: Ashby J. , Ratpan Flora
Published: February 2007

Glycerol formal (GF) has been reported to be teratogenic to the rat. Its mechanism of action in this respect has not been defined, but it has been discussed within the context of its being a possible slow formaldehyde‐releasing agent. In order to evaluate this possibility, the hydrolysis of GF has been studied, and its activity as a mouse bone marrow clastogen assessed using the micronucleus assay. Neither was hydrolysis observed, nor was the test agent active as a clastogen in vivo. It is therefore concluded that the teratogenic activity of GF is unlikely to be associated with the release of formaldehyde in utero. However, GF bears a close structural similarity to the rodent teratogen, ethyleneglycol monomethylether (EGME), and this may provide a basis for understanding its teratogenic activity and for predicting similar activity for other cyclic ether alcohols.
Mutagenesis of L5178Y/TK+ / − −3.7.2C mouse lymphoma cells by the clastogen ellipticine
Authors: Moore Martha M. , Brock Karen H. , Doerr Carolyn L. , Demarini David M.
Published: February 2007

Ellipticine is a potent clastogen in CHO cells (Bhuyan et al: Cancer Res 32:2538–2544, 1972). The reported mutant frequencies produced by ellipticine at the hprt locus in CHO cells are ⩽50/106 survivors (background ∽ 2/106; survival = 10%) (DeMarini et al: Cancer Res 43:3544–3552, 1983; Singh and Gupta: Cancer Res 43:577–584, 1983; Environ Mutagen 5:871–880, 1983). In the present study, the mutagenic and clastogenic activities of ellipticine were evaluated in L5178Y/TK+/− −3.7.2C mouse lymphoma cells. Unlike the results at the hprt locus, ellipticine is a potent mutagen at the tk locus, with as little as 50 ng/ml producing an induced mutant frequency of 142/106 survivors (background = 56/106; survival = 61 %) and 198/106 survivors (background = 72/106; survival = 50%) in two separate experiments. This same dose of ellipticine induced 44 aberrations per 100 metaphases (background = 5/100 cells). At 400 ng/ml, ellipticine induced over 1,000 mutants /106 survivors at ∽ 10% survival and produced 242 aberrations/100 cells. Under the test conditions, most of the aberrations were chromosome rather than chromatid events. As expected for a compound acting primarily by a clastogenic mechanism, almost all of the TK‐deficient mutants were small colonies. Thus, ellipticine is a potent clastogen in both Chinese hamster cells and in mouse lymphoma cells; however, it is a potent mutagen at only the tk locus and not at the hprt locus. These results support.
Coffee is highly mutagenic in the L‐arabinose resistance test in Salmonella typhimurium
Authors: Dorado Gabriel , Barbancho Manuel , Pueyo Carmen
Published: February 2007

The present study shows that the L‐arabinose resistance test in Salmonella typhimurium detects coffee as a strong mutagen in the absence of mammalian microsomal activation. The response of the Ara forward mutation assay was 8.5 times higher than that of TA104, which is the most sensitive to coffee of the tester strains of the Ames test. Both the mutagenesis protocol (preincubation test) and the additional genetic characteristics of the bacterial tester strain (excision repair deficiency, normal lipopolysaccharide barrier, and the presence of plasmid pKM101) were critical factors in the optimal induction by coffee of forward mutations to L‐arabinose resistance. All ten samples of roasted coffee analyzed with the Ara assay were highly mutagenic: one cup of coffee (150 ml) was calculated to induce 3‐4 × 106 AraR mutants. In contrast, coffee prepared from unroasted beans (green coffee) had no mutagenic activity. Regular‐ and sugar‐roasted coffees showed similar mutagenicities, but the specific mutagenic activity of instant coffees (1559 AraR mutants/mg) was almost 2 times that of noninstant ones (834 AraR mutants/mg). The Ara assay allowed the direct testing of coffee, although it was demonstrated that lyophilization has no effect on the mutagenicity of this beverage. Like roasted coffee, roasted barley induced a large number of AraR mutants per mg (227), though its specific mutagenic activity was approximately 4 and 7 times lower than that of noninstant and instant coffees, respectively.
Lack of induction of nuclear aberrations by captan in mouse duodenum
Authors: Chidiac Peter , Goldberg Mark T.
Published: February 2007

The fungicide, captan, is known to induce point mutations in vitro. In extremely high doses, technical grade captan leads to duodenal tumors in mice. In short‐term in vivo assays for genotoxicity, equivocal results have been obtained with captan. In this study, the genotoxicity of captan was studied in vivo in the proximal small intestine of the mouse, the site of its oncogenicity. Orally administered captan up to 4,000 mg/kg body weight failed to induce a response in the small intestine nuclear aberration assay in a wide range of doses under a variety of experimental conditions, including pretreatment of animals with L‐buthionine‐S, R‐sulfoximine (an inhibitor of glutathione biosynthesis). 1,2,3,6‐Tetrahydrophthalimide and bis (trichloromethyl)disulfide, two compounds that have been identified as impurities in technical grade captan, also failed to produce positive results in this assay.
Acrylamide: Induction of heritable translocations in male mice
Authors: Shelby M. D. , Cain K. T. , Cornett C. V. , Generoso W. M.
Published: February 2007

Acrylamide (AA), known to induce dominant lethals in male rodents, was studied in the mouse heritable translocation test by using intraperitoneal injections on 5 consecutive days. Matings on days 7‐10 following the last injection yielded a high frequency of translocation carriers in the F1 male population, which demonstrated that acrylamide is an effective inducer of translocations in postmeiotic germ cells. As an inducer of both dominant lethals and heritable translocations in late spermatids and early spermatozoa, AA is similar to alkylating agents such as ethylmethanesulfonate and ethylene oxide. However, AA′s chemical structure, the nature of adducts formed with DNA, and its lack of mutagenicity in bacteria suggest a different mechanism as the basis for AA′s germ cell mutagenicity.
Effects of radiofrequency radiation and simultaneous exposure with mitomycin C on the frequency of sister chromatid exchanges in chinese hamster ovary cells
Authors: Ciaravino Victor , Meitz Martin L. , Erwin David N.
Published: February 2007

Chinese hamster ovary (CHO) cells were exposed for 2 hr with and without mitomycin C (MMC) (1 × 10−8M) to pulsed wave radiofrequency radiation (RFR) at 2450 MHz. The repetition rate of 25,000 pulses per sec (pps), pulse width of 10 μs, and exposure geometry used, resulted in a specific absorption rate (SAR) of 33.8 W/kg. The following exposure regimens were used: 1) a 37°C water bath control; 2) a water bath temperature control (TC) in which the continuously monitored medium temperature closely followed the temperature rise in the RFR‐exposed flasks; and 3) the RFR‐exposed cells in a water bath set at 37°C prior to exposure. RFR exposure resulted in a maximum cell culture medium temperature of 39.2°C. In the absence of MMC, there was no significant increase in sister chromatid exchange (SCE) in the RFR‐exposed or TC groups over that of the 37°C control. When a simultaneous treatment of RFR and MMC occurred there was no statistical difference in SCE frequency from that caused by chemical treatment alone.
Vaporization technique to measure mutagenic activity of volatile organic chemicals in the ames/Salmonella assay
Authors: Hughes Thomas J. , Simmons Debra M. , Monteith Linda G. , Claxton Larry D.
Published: February 2007

The purpose of this research was to develop and characterize a sensitive test method to detect mutagenic activity of volatile liquid organic chemicals (i.e., volatiles) in the Ames/Salmonella assay. A Tedlar® bag vaporization technique was developed, which increased contact time between the volatiles and bacterial test system, circumvented volatilization limitations in the standard plate incorporation and preincubation methods, allowed chemical analysis during incubation, and was flexible in design.

The vaporization technique was evaluated concurrently against the plate incorporation and preincubation techniques with eight liquid volatile mutagens in the Ames/Salmonella mutagenicity assay with Salmonella typhimurium strains TA100 and TA102. Results suggested that when volatile organic chemicals with boiling points below 63 °C were tested for mutagenic activity, the most sensitive test conditions were the vaporization technique with TA100. GC analysis of epichlorohydrin and butylene oxide concentrations within Tedlar® bags suggested that these two chemicals volatilized and were contained in the media after 1 hr of incubation at 37 °C. The mutagenic activity of six volatile liquid mutagens was similar in single and triple plate Tedlar® bags.

Three general test groups of volatile organic chemicals were identified by test data: 1) chemicals which had boiling points below 63°C, for which the vaporization technique was the most sensitive test procedure (ethylene, propylene, and butylene oxides and methylene chloride); 2) chemicals which had boiling points from 1077 to 132°C, for which the vaporization technique was still useful, but where sensitivity was only slightly increased over the preincubation technique (1‐bromo‐2‐chloroethane, epichlorohydrin, and ethylene dibromide); and 3) a chem‐.
Micronucleus assay in human fibroblasts: A measure of spontaneous chromosomal instability and mutagen hypersensitivity
Authors: Rudd Noreen L. , Hoar David I. , Greentree Carol L. , Dimnik Leo S. , Hennig Ursula G. G.
Published: February 2007

By comparing fibroblast strains derived from individuals exhibiting chromosome instability and/or mutagen hypersensitivity (Cockayne syndrome, ataxia telangiectasia, and Fanconi anemia) with strains derived from healthy donors, the fibroblast micronucleus assay has been established as a reproducible measure of the genotypic variation in spontaneous or mitomycin C (MMC)‐induced chromosomal instability. The patient strains that were moderately or exquisitely sensitive to MMC could be distinguished readily from the control strains, both in levels of spontaneous micronuclei (probably related to chromosome breakage) and in sensitivity to MMC, whereas the mildly sensitive strain (Cockayne syndrome) overlapped with the control range. The reproducibility of the assay was evaluated within and between experiments. Paired comparison analyses between duplicate cultures and between repeat experiments failed to show any significant differences between micronucleus frequencies within strains, whereas a significant difference in the spontaneous micronucleus frequencies between strains was observed. In addition to its value as a test system for genotoxins, the fibroblast micronucleus assay may be useful for investigating genetically determined hypersensitivity to mutagens, elevated spontaneous chromosomal breakage, and chromosome segregation errors.
Mutagenicity of products generated by the reaction between several antiparasitic drugs and nitrite
Authors: Alba M. Arriaga , Espinosa J. , De Nava C. Cortinas
Published: February 2007

Drugs containing secondary aliphatic amines, heterocyclic nitrogen, or secondary aliphatic amido groups (chloroquine, dehydroemetine, mebendazole, and piperazine) and pyrimidine derivatives such as pyrantel pamoate were reacted in vitro with sodium nitrite at pH 3.7 and became mutagenic for Salmonella typhimurium strain TA1535. The products derived from the nitrosation of chloroquine and dehydroemetine required metabolic activation by mammalian hepatic S9 to be mutagenic. The N‐nitroso derivatives of mebendazole, piperazine, and pyrantel pamoate were mutagenic with and without S9, although more activity was noted in the presence of S9 with the nitrosated compounds formed from mebendazole and piperazine. Under identical conditions, no mutagenic products were detected from quaternary ammonium salts such as bephenium hydroxynaphthoate or drugs containing tertiary heterocyclic amino groups, such as iodochlorhydroxyquin.
Responses of the l5178y tk+/tk− mouse lymphoma cell forward mutation assay: III. 72 Coded chemicals
Authors: McGregor Douglas B. , Brown Alison , Cattanach Pamela , Edwards Ian , McBride Douglas , Riach Colin , Caspary William J.
Published: February 2007

Seventy‐two chemicals were tested for their mutagenic potential in the L5178Y tk+/− mouse lymphoma cell forward mutation assay, using procedures based upon those described by Clive and Spector (Mutat Res 44:269‐278, 1975) and Clive et al. (Mutat Res 59:61‐108, 1979). Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 μg/ml. The chemicals were tested at least twice. Significant responses were obtained with allyl isothiocyanate, p‐benzoquinone dioxime, benzyl acetate, 2‐biphenylamine HCl, bis(2‐chloro‐1‐methylethyl)ether, cadmium chloride, chlordane, chlorobenzene, chlorobenzilate, 2‐chloroethanol, chlorothalonil, cytarabine‐HCl, p,p′‐DDE, diazinon, 2,6‐dichloro‐p‐phenylenediamine, N,N‐diethylthiourea, diglycidylresorcinol ether, 2,4‐dimethoxy aniline‐HCl, disperse yellow 3, endosulfan, 1,2‐epoxyhexa‐decane, ethyl acrylate, ethyl benzene, ethylene thiourea, F D and C yellow Number 6, furan, heptachlor, isophorone, mercuric chloride, 4,4′‐methylenedianiline 2 HCl, methyl viologen, nickel sulfate‐6H2O, 4,4′‐oxydianiline, pentachloroethane, piperonyl butoxide, propyl gallate, quinoline, rotenone, 2,4,5,6‐tetrachloro‐4‐nitro‐anisole, 1,1,1,2‐tetrachloroethane, trichlorfon, 2,4,6‐trichlorophenol, 2,4,5‐trimetho‐xybenzaldehyde, 1,1,3‐trimethyl‐2‐thiourea, 1‐vinyl‐3‐cyclopetene dioxide, vinyl toluene, and ziram.

Apart from 2‐biphenylamine‐HCl, 2‐chloroethanol, disperse yellow 3, ethylene thiourea, FD and C yellow number 6, phenol, and 1,1,2‐tetrachloroethane, rat liver S9 mix was not a requirement for these compounds.

Chemicals not identified as mutagens were acid red, 11‐aminoundecanoic acid, boric acid, 5‐chloro‐o‐toluidine, coumaphos, cyclohexanone, decabromodiphenyl oxide, di(2‐ethylhexyl)adipate, ferric chloride, fluometuron, melamine, monuron, phenesterin, phthalimide, reserpine, sodium dodecyl sulfate, 4,4‐sulfonyldianiline, tetrachloroethylene, and zearalenone.

The assay was incapable of providing a clear indication of whether some chemicals were mutagens; these were benzyl alcohol, 1,4‐dichlorobenzene, phenol, succinic acid‐2,2‐dimethyl hydrazide, and toluene.
Persistence of sce‐inducing lesions in lymphocytes of mice exposed to diaziquone
Authors: Kligermana A. D. , Bryant M. F. , Erexson G. L. , Rabinowitz J. R.
Published: February 2007

Male C57B1/6 mice were injected i.p. with either 1.25 or 5.0 mg/kg diaziquone (AZQ) and killed at various time intervals from 1 to 99 days post treatment for examination of sister chromatid exchange (SCE) persistence in the peripheral blood lymphocytes (PBLs) and splenocytes. SCE frequencies were found to decay steeply during the first week after exposure in both PBLs and splenocytes. This pattern was followed by a slower decline to baseline over the next week. However, high‐frequency cell (HFC) analysis indicates that significant numbers of HFCs persist in the PBLs through day 28 and splenocytes at day 99 post exposure. Mathematical modeling of the time‐response curves indicates that the average life span of the majority of AZQ‐induced SCE‐producing lesions in murine PBLs and splenocytes responsive to phytohemagglutinin is between 3 and 5 days.
Mutagenic potency at the na+ /k+ atpase locus correlates with cycle‐dependent killing of 10t1/2 cells
Authors: Smith Gary J. , Grisham Joe W. , Bentley Karin S.
Published: February 2007

Perturbation of DNA replication by chemical‐DNA adducts produced by exposure to mutagenic/carcinogenic chemicals results in mutagenic or cytotoxic damage in the DNA. Demonstration of a correlation between cell cycle dependency of cytotoxicity and point mutation at the Na+/K+ ATPase gene could suggest that the two consequences of chemical exposure are caused by the same damage in the template DNA and that both are mediated through DNA replication‐associated mechanisms. N‐methyl‐N′‐nitro‐N‐nitrosoguanidine, N‐ethyl‐N′‐nitro‐N‐nitrosoguanidine, 4‐nitroquinoline‐1‐oxide, and benzo(a)pyrene‐trans‐7,8‐dihydrodiol‐9, 10‐epoxide demonstrated cell cycle‐related patterns of cytotoxicity in 10T1/2 cells, with maximal cell killing produced by exposure in early S phase, and were highly efficient mutagens of the Na+/K+ ATPase gene relative to their cytotoxic potential. In contrast, methyl methanesulfonate and N‐acetoxy‐N‐2‐fluorenylacetamide were maximally cytotoxic in ceil populations exposed in early G1 phase and were weak mutagens of the Na+/K+ ATPase gene at comparable levels of cytotoxicity. These data suggest that mutagenic/carcinogenic chemicals that are effective at producing mutations by misreplication kill cells by a related mechanism that may be associated with the perturbation of DNA replication.
Proposals for standardized protocols for cytogenetic analyses of acute leukemias, chronic lymphocytic leukemia, chronic myeloid leukemia, chronic myeloproliferative disorders, and myelodysplastic syndromes
Authors: Haferlach Claudia , Rieder Harald , Lillington Debra M. , Dastugue Nicole , Hagemeijer Anne , Harbott Jochen , Stilgenbauer Stephan , Knuutila Sakari , Johansson Bertil , Fonatsch Christa ,   on behalf of the European Leukemia Net–Workpackage Cytogenetics
Published: February 2007

The impact of cytogenetic characterization based on chromosome banding analyses and fluorescence in situ hybridization on clinical decision making has increased dramatically during recent years. Therefore, laboratory techniques have to be optimized to provide reliable results for optimal patient care. In addition, quick and correct results save time and money by preventing unnecessary additional diagnostics and suboptimal treatment approaches. It was our aim to present proposals for standardized protocols to improve the diagnosis, and hence the treatment outcome, of hematologic malignancies. © 2007 Wiley‐Liss, Inc.
Diagnostic imaging in head and neck disease: Current applications of ultrasound
Authors: Scheible F. William , Leopold George R.
Published: February 2007

Diagnostic ultrasound has become firmly established as a key imaging modality in obstetrics and gynecology. Its role in abdominal and retroperitoneal disease is also well known and continues to expand. Although usage of ultrasound in the head and neck had its beginnings many years ago, the advent of newer high‐resolution transducers has allowed for further investigation of diseases in this area. Of particular interest are the thyroid gland and the extracranial carotid arteries. This review summarizes the current utility of gray‐scale and real‐time ultrasound in evaluating head and neck disease, and discusses potential future applications of the modality.
Disability and rehabilitation in head and neck cancer patients after treatment
Authors: Olson Marian L. , Shedd Donald P.
Published: February 2007

In an effort to obtain quantitative and qualitative information regarding the extent of disability sustained following definitive treatment for head and neck cancer, 51 patients–28 who had had laryngectomy and 23 who had had other major surgery–were interviewed. Also examined were the types of rehabilitation measures taken. In all cases, the following areas in which disability could occur were identified and explored: physical appearance, speech, deglutition, mastication, salivation, sensory deficits, cranial motor‐nerve deficits, pain, nutrition, activities of daily living, psychosocial functioning, vocational status, environmental parameters, and delayed complications. Where appropriate, ratings and delineations of severity were compiled. Nine methods of rehabilitation were assessed with regard to frequency of utilization: surgical reconstruction, dental‐maxillofacial prosthetics, speech therapy, physical therapy, rehabilitation nursing, occupational therapy, vocational rehabilitation, rehabilitation counseling, and social service. Our conclusions were that half of the patients studied had sustained significant disability in three to four areas, while 43% had moderate or severe disability in five to nine areas. Additionally, the head and neck surgeon was found to have used surgical reconstructive and dental‐maxillofacial prosthetic measures, as well as the services of seven categories of allied health professionals, to provide rehabilitation.
The pathology of head and neck tumors: Salivary glands, part 1
Authors: Batsakis John G. , Regezi Joseph A.
Published: February 2007

The surgical pathology of the head and neck is perhaps the most demanding of all subdivisions of pathology. It is demanding both for the pathologist and for the head and neck surgeon–who, as a team, must provide optimal patient care. Beginning with this issue of HEAD & NECK SURGERY, a series will be presented dealing with the clinicopathologic aspects of head and neck tumors. The authors have chosen to begin with the salivary glands, and in this report they present a concept of histogenesis and classification as well as an analysis of (1) salivarygland tumors in children, (2) the relationship between breast carcinoma and salivary‐gland carcinoma, (3) the status of radiation induction of salivary‐gland tumors, and (4) the clinicopathologic aspects of tumors of the salivary oncocyte.
Neurilemoma of the larynx: A case study
Authors: Nanson Eric M.
Published: February 2007

Neurilemoma of the larynx is not common. Thus far, 86 cases have been described in the literature. In this study, another case, occurring in a 67‐year‐old woman, is discussed. The potential danger of the lesion is emphasized. The most common nerve of origin is thought to be the internal branch of the superior laryngeal nerve. Removal via a lateral pharyngotomy is advocated for larger tumors.
Temporal artery‐based forehead flap
Authors: Mathog Robert H. , Smith Raymond O.
Published: February 2007

The historical development of the forehead flap is reviewed, and an operative experience using delayed and nondelayed techniques in 30 cases is described. The reliability of the forehead flap is evaluated with regard to patient morbidity and correction of deformity and dysfunction in such sites as the cheek, lip, corner of the mouth, floor of the mouth, tongue, pharyngeal wall, and tonsil. Analyses include length of hospital stay and complications, as well as the relationship of these factors to the methods employed in the reconstructive processes. The advantages and disadvantages of the various techniques are illustrated using individual cases.
Chemosurgery for the microscopically controlled excision of cutaneous cancer
Authors: Mohs Frederic E.
Published: February 2007

Cancer of the skin and of other accessible structures can be removed under complete microscopic control if the cancerous area is excised layer by layer, and if the undersurface of each layer is then examined under the microscope through systematic use of frozen sections. If the cancer is extensive and complicated, or if the neoplasm is of a type that is readily disseminated, the tissues are fixed in situ with zinc chloride prior to the excision of each layer (fixed‐tissue technique). If the cancer is not overly extensive or complicated, the layers of tissue are excised in the fresh, unfixed state (fresh‐tissue technique). Both methods are highly reliable. In two consecutive series of basal‐cell carcinomas treated chemosurgically, the five‐year cure rate achieved was 99.3% for the 9,351 lesions removed by the fixed‐tissue technique, and 98.1% for the 196 lesions removed by the fresh‐tissue method.
Electron microscopy in the diagnosis of head and neck tumors
Authors: Battifora Hector , Applebaum Edward L.
Published: February 2007

Six patients with malignant head and neck tumors are shown to have required electron microscopy for accurate diagnosis. In all of these tumors, there were ultrastructural features of cytodifferentiation that were not discernible by light microscopy, such as neurosecretory granules, desmosomes, cytoplasmic processes, tonofibrils, and myofilaments. Electron microscopy is helpful in the differential diagnosis of tumors in general, but its effectiveness is particularly apparent in small‐cell “undifferentiated” tumors such as neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma, undifferentiated squamous‐cell carcinoma of the lymphoepithelioma type, and malignant lymphoma. It has also been helpful in the identification of amelanotic melanoma and spindle‐cell carcinoma.
The pathology of head and neck tumors: Salivary glands, part 3
Authors: Batsakis John G. , Regezi Joseph A. , Bloch Daniel
Published: February 2007

The term adenoma is applied to a rather wide variety of histopathologic entities in the salivary glands. These include tumors derived from the ductal epithelium and/or from myoepithelial cells and other salivarygland elements, such as the sebaceous glands. Within the categories of mixed tumor (pleomorphic adenoma), monomorphic adenoma, clear‐cell tumor, and sebaceous lesions, there are also several subtypes, each of which lends further credence to the germinative potential of the salivary tissues. Presented in this report is a clinicopathologic and histogenetic analysis of these lesions. Specifically discussed are mixed tumor, monomorphic adenoma, carcinoma ex‐pleomorphic adenoma, clear‐cell tumor, sebaceous lymphadenoma, and sebaceous carcinoma.
Embryonic development of the head and neck: Part 1, an overview
Authors: Wilson Doris B.
Published: February 2007

Current research problems and approaches to the embryonic development of the head and neck are surveyed and discussed in terms of congenital defects that occur in this region. Of particular significance are new interpretations of the contributions the neural crest cells make to various components of the head and neck, the influence that the brain and notochord exert on the overall morphology of the head region, the tissue interactions involved in the development and differentiation of the pituitary gland (hypophysis), and the significance of vascular perturbations with respect to malformations in the craniofacial region.
Epidemiology of cancer of the nose and paranasal sinuses: Current concepts
Authors: Roush George C.
Published: February 2007

Cancer of the nose and paranasal sinuses (SNC) has been attributed to occupational exposure to nickel, chromium, radium dichlordiethyl sulphide, isopropyl oil, and hydrocarbons. Occupational groups with an increased SNC risk include furniture, boot and shoe workers, and workers in U.S. counties heavily involved in both petroleum and chemical manufacturing; specific agents have not been identified with certainty. In most of the studies, the risk for developing SNC in the exposed workers was 21 to 100+ times greater than the risk for SNC in those who were not exposed. Undifferentiated and squamous histologies are associated with nickel refining; adenocarcinomas are found in woodworkers, boot and shoe manufacturers, and textile workers. Most occupations at risk for SNC were also at risk for cancer of other sites, particulary lung and skin cancer. Study of the epidemiology of SNC may identify unrecognized carcinogens and occupational groups at increased cancer risk.
Melanoma of the conjunctiva—A rational approach to management
Authors: Birns Jeffrey W. , Jenkins Herman A.
Published: February 2007

Eleven of 12 patients treated for invasive melanomas of the conjunctiva at the UCLA Hospitals from 1955 to 1976 revealed data sufficient for evaluation. Of these 11 cases, 4 died from 3 to 13 years after treatment as a result of the disease. The plan presented for surgical management of melanosis is based on histologic criteria and on the anatomic location of the tumor. In this series, such management ranged from local excision of noninvasive melanotic lesions to orbital exenteration with parotidectomy and radical neck dissection for invasive melanomas that involved the palpebral conjunctiva or caruncle. Extended follow‐up is needed in all patients.
Head and neck cancer—Emotional management
Authors: Herzon Fred S. , Boshier Maureen
Published: February 2007

The complete care of a patient with head and neck cancer should attend to the emotional as well as the physical aspects of the disease; usually the physical component of the disease is emphasized, while care of the emotional response of the patient and family is rarely addressed. There is no single, caring way to respond or cope with the emotional aspects of this disease. Nonetheless, it should be underscored that communication between the providers of health care (i.e., physician, nurse, aid, therapist, etc.) and the patient and family should be maintained during all phases of care. This article describes an approach to providing emotional support to cancer patients and their families during the phases of initial diagnosis and treatment, posttherapy, rehabilitation, recurrence, dying, and death. The emotional response of the health care provider in these circumstances is also addressed.
Role of chemotherapy in head and neck cancer: Systemic use of single agents and combinations in advanced disease
Authors: Muggia Franco M. , Rozencweig Marcel , Louie Arthur E.
Published: February 2007

Chemotherapy of head and neck cancer has recently been receiving increasing attention as a treatment modality. The basis for this interest has been the availability of at least three agents with reproducible antitumor activity: methotrexate, bleomycin, and cisplatinum (diamminedichloroplatinum). These agents alone or in combination have been demonstrated to be of palliative value in patients whose disease recurs or is too advanced for other therapeutic modalities. Although the multiple drug regimens used have not been curative, their relative effectiveness has raised hopes that, in combination with other modalities, they may lead to improvements in survival and in local control in earlier stages of disease. In addition, as a result of multimodality approaches, it is hoped that it may be possible to identify the role of chemotherapy and specific agents in the treatment of various sites of origin of these tumors. The interaction of chemotherapy and radiation—and the use of intraarterial chemotherapy—fall beyond the scope of this review but constitute another important aspect for investigation in the treatment of these malignancies.
Embryonic development of the head and neck: Part 4, organs of special sense
Authors: Wilson Doris B.
Published: February 2007

A synopsis of the embryonic development of the eye, the ear, and the olfactory organ and taste buds is presented. The eye is discussed in terms of the sensory and nonsensory portions of the eyeball and of such associated structures as the extrinsic eye muscles, eyelids, conjuctiva, and lacrimal apparatus. The embryology of the internal, middle, and external ear is reviewed, as well as positional changes of both the eye and ear relative to other structures of the head and neck. Various congenital defects affecting the eye and ear are also discussed.
An adjunctive technique to rhinoplasty of the aging nose
Authors: Kabaker Sheldon S.
Published: February 2007

This report presents a simple, valuable adjunct to rhinoplasty in the specific case of senile elastosis. This type of skin will not contract as in younger individuals, and tip ptosis is quite often a problem in the senile nose. Described is a semilunar skin excision of the nasal dorsum in a large nose undergoing primary or revisionary rhinoplasty. Correction of tip ptosis occurring many years after rhinoplasty or its prevention in large, elderly noses undergoing rhinoplasty is presented.
Embryonic development of the head and neck: Part 5, the brain and cranium
Authors: Wilson Doris B.
Published: February 2007

The development of the brain is presented with respect to closure of the neural tube, the formation of the five vesicles of the brain and their derivatives, and the cranial flexures. The cranial nerves, meninges, choroid plexuses, and cerebral vasculature are also discussed. The origin and ossification of the bony elements of the head and neck, including the neurocranium, viscerocranium, and cervical vertebrae, are described, as well as major congenital defects of the brain and the cranium.
Myocutaneous flaps for head and neck reconstruction
Authors: Ariyan Stephan , Cuono Charles B.
Published: February 2007

The recent development of myocutaneous flaps has ushered in an era of one‐stage reconstructions, which have changed the patterns of surgery for head and neck cancer. This article reviews the development of these flaps and the clinical applications at various sites of the head and neck. Personal experience with 31 consecutive myocutaneous flaps confirms the versatility and reliability of these new techniques.
Ossification of decalcified and nondecalcified homologous bone grafts
Authors: Rafaty F. Mark
Published: February 2007

This two‐year study examined the process of reossification and survival of decalcified and nondecalcified bone grafts implanted under the scalp tissue of 15 rabbits. Both radiologic and histologic examination showed that the nondecalcified fresh‐frozen bone specimens became totally viable and recalcified while largely retaining their initial size. The decalcified bones, however, were totally absorbed within a period of four months. Possible reasons for failure of the decalcified bone to reossify are discussed.
The pathology of head and neck tumors: Nasal cavity and paranasal sinuses, part 5
Authors: Batsakis John G.
Published: February 2007

Nasal polyps and epithelial papillomas of the sinonasal tract often manifest similar clinical signs and symptoms. The similarity ends, however, when one considers their disparate biologic behavior. Polyps are associated with atopy, infection, and some metabolic, systemic disorders, whereas papillomas are enigmatic in pathogenesis and do not have an association with possible precursor disorders. While recurrences of nasal polyps may be an annoyance for the patient, such recurrences lack the local aggressiveness of the papilloma. Malignancies are rare in nasal polyps, whereas the frequency of malignancies in papillomas is both statistically and biologically significant. In this report, selected aspects of nasal polyps are considered and serve to contrast with the clinicopathologic evaluation of epithelial papillomas.
Relative risk factors in the treatment of juvenile nasopharyngeal angiofibroma
Authors: Cummings B. J.
Published: February 2007

The potentially fatal complications associated with surgery and radiation therapy in the management of juvenile nasopharyngeal angiofibroma (JNA) are analyzed. Quantitative risk factors established from review of the literature suggest a risk of potentially fatal complications of 1 in 3,000 from general anesthesia, 1 in 1,600 from arteriography, 1 in 160 from blood transfusion, and 1 in 500 from the surgical procedure itself. The total of these risks is comparable to the 1% lifetime risk of developing a radiation‐induced tumor after radiation therapy. The time pattern of these complications differs in that fatal radiation‐induced complications are delayed, whereas the risks associated with surgery, general anesthesia, and blood transfusion are more immediate. However, it is suggested that treatment‐related risks of fatal complications are of a similar order of magnitude for surgery and for radiation therapy in the management of JNA.
Trapezius osteomyocutaneous island flap for reconstruction of the anterior floor of the mouth and the mandible
Authors: Panje William , Cutting Court
Published: February 2007

The anterior mandible defect following cancer excision presents a formidable reconstructive challenge. A trapezius osteomyocutaneous island flap based on the transverse cervical vessels is described which allows immediated reconstruction of the entire defect. The various classes of bone flaps retaining an intact vascular pedicle are discussed. The osseous extension of the trapezius island flap appears to be adequately perfused. The anatomy involved and the orthopedic sequelae of using this flap are discussed.
The fourth branchial cleft anomaly
Authors: Shugar Martin A. , Healy Gerald B.
Published: February 2007

The fourth branchial cleft anomaly has long been postulated. A case in which a lower neck sinus tract extended under the clavicle near the subclavian vessels is presented. The distinguishing features of bronchogenic and branchogenic anomalies are discussed. It appears that unless a complication (e.g., abscess, inflammatory process) of the fourth branchial cleft sinus tract occurs within the mediastinum, mandating full exploration, the complete form of the anomaly may continue to remain undocumented.
Transnasal correction of choanal atresia
Authors: Feuerstein Sidney S. , Krespi Yosef P. , Sachdev Ranjit K.
Published: February 2007

A simple life‐saving modification of the transnasal approach, which does not require endotracheal anesthesia or preoperative tracheostomy, is described. The use of polyethylene tubes, flanged at the distal end and split at the proximal end, is the most significant feature of this technique. In 14 of the 16 cases of choanal atresia presented, this was the definitive corrective procedure, and further revisions or a later transpalatal approach were not required. The advantages of this technique are that it is simple, it may be used in the first 24 hours of life or at any age, the patient may be released from the hospital in 1 to 2 weeks, and minimal postoperative care is required.