bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation in sister chromatid exchange frequencies between human and pig whole blood, plasma leukocyte, and mononuclear leukocyte cultures
Authors: Larramendy Marcelo L. , Reigosa Miguel A.
Published: February 2007

Sister chromatid exchange (SCE) induction by ultraviolet (UV) light was studied in both human and pig whole blood cultures (WBC) and plasma leukocyte cultures (PLC). No variation in SCE frequency was observed between pig WBC and PLC in control as well as in treated cells. Conversely, SCE frequencies of human PLC were consistently higher than those of WBC in control and UV‐exposed cells. Thus, red blood cells (RBCs) do not influence the sensitivity of lymphocytes to UVlight exposure, and there must be some different culture condition(s) in the induction of SCEs between human WBC and PLC but not in swine lymphocyte cultures. Since the BrdUrd/lymphocyte ratio of WBC was halved in PLC, the effect of BrdUrd concentration in inducing the SCE baseline frequency of PLC may be ruled out. Also, Ficoll‐Hypaque‐separated human mononuclear leukocytes in culture (MLC), but not pig MLC, showed a two‐fold increase in SCE frequency over WBC values. Thus, neither the cell separation technique nor polymorphonu‐clear leukocytes had a significant role in the elevated SCE frequency of human PLC or MLC. Experiments where human RBCs were titrated into human PLC showed that the induction of an elevated SCE frequency of PLC was suppressed in a dose‐dependent manner by the presence of RBCs in the culture medium. Since the incorporation of pig or human RBCs into human PLC as well as into MLC reduced the SCE frequency to that of WBC, a common component and/or function existing in these cells is suggested. Analysis of different RBC components showed that RBCs, specifically RBC ghosts, release a diffusible but not dialyzable “corrective” factor into culture medium that is able to reduce the SCE frequencies of PLC. Antioxidant enzymes such as catalase and horseradish peroxidase were unable to reduce the SCE frequency of human PLC to WBC values.
NPPD (Spy dust) is predicted to be a mutagen
Authors: Klopman Gilles , Kalos Alex , Frierson Manton , Rosenkranz Herbert S.
Published: February 2007

With the aid of CASE, the Computer Automated Structure Evaluation system, a new artificial intelligence procedure to study structure‐activity relationships and a data base consisting of 233 monocyclic nitroarenes, it is predicted that 5‐(4‐nitrophenyl)‐2,4‐pentadienal will be mutagenic for Salmonella typhimurium but that the activity will be very low.
Patterns of mutagen binding and penetration in multicell spheroids
Authors: Olive Peggy L.
Published: February 2007

Mutagen damage to a cell located at some distance from the site of application of the mutagen will depend, in part, on how effectively it can penetrate through cells composing different tissues. Chinese hamster V79 spheroids were used to model mutagen “penetrability” by providing several layers of cells growing with tissue‐like packing. By treating cells of intact and trypsin‐dissociated spheroids at the same drug‐to‐cell ratio, an estimate relative sensitivity to nine mutagens was determined. The effective toxicity index (ETI) was defined as the ratio of the concentrations of mutagen required to kill 50% of cells (measured after a 1‐hr treatment at 37°C) in dissociated versus intact spheroids and similarly for mutation at the HGPRT locus (EMI). Values for ETI were consistent with values for EMI and varied from 0.01 for 4NQO to 2 for AF‐2. Direct information on mutagen penetration was obtained for fluorescent mutagens by flow cytometry. Values for EFI (effective fluorescence index) varied from 0.07 for Hoechst 33342 to 1 for AF‐2. These results can be interpreted as reflecting differences in ability of mutagens to penetrate spheroids; some direct‐acting mutagens are likely to be effective only near their site of application (ie, UV, Hoechst 33342, 4NQO) while others are able to penetrate through successive cell layers with little difficulty (ie, monobromobimane, AF‐2).
Chromium (VI) comutagenesis: Characterization of the interaction of K2CrO4 with azide
Authors: Lavelle James M.
Published: February 2007

In a previous report chromate potentiated the mutagenicity of sodium azide, apparently by affecting repair and/or replication of DNA. Further evidence in support of such a mechanism for chromate potentiation is reported here. Chromate does not react directly with azide or its major mutagenic metabolite, azidoalanine, eliminating such reactions as possible mechanisms for potentiation. Further, azide was unable to potentiate the mutagenicity of chromate in Salmonella typhimurium strain TA104, which is sensitive to chromate mutagenicity but not to azide. Thus, it appears that the potentiation is not due to an action of azide in modulating chromate mutagenicity. Finally, the interaction was not altered by deficiency in recA gene product in S typhimurium GW19, nor by enhancement of SOS repair in the pKM101 containing strain TA100. Thus, induction of recA‐dependent functions seems to play no role in the comutagenic actions of chromate. The simplest explanation for potentiation seems to be that chromate is able either to limit error‐free recovery from azide‐induced DNA damage or to promote error‐prone repair or error‐prone processing at sites of lesions.
Evaluation of the effect of agar on the results obtained in the L5178Y mouse lymphoma assay
Authors: Meyer Mary , Brock Karen , Lawrence Kay , Casto Bruce , Moore Martha M.
Published: February 2007

The L5178Y TK+/− mouse lymphoma assay is widely used in mutagenicity testing. Trifluorothymidine‐resistant (TFTr) mutants are quantitated following growth in agar‐supplemented cloning medium. In an attempt to evaluate the effect of agar on plating efficiency, we have tested several lots of Difco Noble agar (cat. No. 0142‐01‐8; normally used in this assay) and compared it with Baltimore Biological Laboratory (BBL) agar (cat No. 11849). We find that BBL agar gives a higher and less variable plating efficiency than any of the Noble lots tested. Colonies plated in BBL agar tend to appear significantly earlier on the plates than those cloned in Noble agar. The absolute mutant number and the induced mutant frequency quantitated from a treated culture is generally higher in BBL compared to Noble agar. To determine if this higher frequency is due to increased mutant recovery rather than “sneak through” of nonmutant cells, we isolated 97 mutants from treated cultures (44 large colonies and 53 small colonies) and 69 mutants from untreated cultures (24 large colonies and 45 small colonies) and tested them for TFT resistance. All but one (a large colony from an untreated culture) were found to be TFTr, indicating that the mutant frequency is due to an increased mutant recovery. The spontaneous mutant frequency was quantitated for 122 untreated cultures. Showing little variation within and between experiments, the spontaneous mutant frequency yielded a mean of 57.7, with a standard deviation of 14.4. Under our laboratory conditions, BBL agar gave reliable results, and we prefer it for use in cloning L5178Y mouse lymphoma cells.
A protocol for the combined biochemical and serological identification of the Ames mutagen tester strains as Salmonella typhimurium
Authors: Busch David B. , Archer John , Amos Effie A. , Hatcher James F. , Bryan George T.
Published: February 2007

Previously published reports have noted biochemical reactions atypical of Salmonella among the Ames tester strains of Salmonella typhimurium, and an inability to assign the strains to a specific Salmonella O (heat‐stable cell wall) antigen group. We studied the biochemistry and serology of strains TA97, 98, 100, 102, 104, 1535, 1537, and 1538 in an attempt to develop a protocol to correctly speciate the strains. Biochemical reactions of all eight strains using standard media supplemented with histidine and biotin were consistent with those of the genus Salmonella. Strains TA100, 104, and 1535 were assigned to Salmonella O groups using bacteria treated with hot ethanol (White schema). H (flagellar) antigen assignments were performed successfully with seven of the eight strains. Two H antigen assignments required the use of the Craigie tube test for selection of motile revertants. Combining our biochemical and serological results obtained by this protocol, we were able to correctly speciate TA100, 104, and 1535 as Salmonella typhimurium. Our results demonstrate that representatives of the tester strains can be correctly speciated provided that procedures are followed that allow for the unusual nutrient requirements, the deep rough cell wall mutation, and the variably deficient motility of these organisms.
An evaluation of the genotoxic potential of di‐isononyl adipate
Authors: McKee R. H. , Lington A. W. , Traul K. A.
Published: February 2007

Di‐isononyl adipate (DINA) is one of a group of adipates used primarily as plasticizers. Concern over the mutagenic and carcinogenic potential of these materials was stimulated by the finding that one member of this class, di‐(2‐ethylhexyl) adipate (DEHA), induced liver tumors in female mice in a chronic feeding study. Accordingly, the genotoxic potential of DINA was evaluated in a battery of in vitro tests including the Salmonella/mammalian microsome mutagenicity assay, the mouse lymphoma TK +/u assay, and two tests of morphologic transforming ability, the BALB 3T3 and the Syrian hamster embryo in vitro transformation assays. DINA did not exhibit any evidence of mutagenic or transforming potential in any of the assays utilized.
Mutagenicity of N‐substituted phenanthrene 9,10‐imines in Salmonella typhimurium and Chinese hamster V79 cells
Authors: Glatt Hansruedi , Shtelzer Sarah , Sheradsky Tuvia , Blum Jochanan , Oesch Franz
Published: February 2007

We previously showed that some (nonsubstituted) aziridines derived from polycyclic aromatic hydrocarbons (arene imines) elicit various mutagenic and genotoxic effects in bacteria and mammalian cells and that these arene imines are active at much lower concentrations than the corresponding epoxide analogues. In the present study, N‐substituted derivatives of phenanthrene 9,10‐imine were investigated. All 10 derivatives studied showed direct mutagenicity in Salmonella typhimurium TA100. Some of the compounds additionally exhibited weak effects in the strains TA98 and TA1537. Most N‐substituted derivatives were weaker mutagens than unsubstituted phenanthrene 9,10‐imine but stronger mutagens than phenanthrene 9,10‐oxide. Bulky substituents reduced the mutagenicity more than did small substituents. In addition, the derivatives with electron‐withdrawing substituents (with the exception of N‐chlorophenanthrene 9,10‐imine) were weaker mutagens than those with electron‐donating substituents. Phenanthrene 9,10‐imine and five N‐substituted derivatives were investigated to determine whether they induce gene mutations at the hgprt locus in V79 cells. Four compounds, including the parent aziridine, were positive in the V79 test. The other two compounds were negative. The mutagenic potencies in the V79 cell system did not correlate well with those obtained with the Salmonella system. Overall, the study shows that in addition to unsubstituted arene imines, N‐substituted derivatives are mutagenic. This finding is of interest, as metabolic pathways leading from aromatic compounds to N‐substituted arene imines are conceivable.
Dominant visible and electrophoretically expressed mutations induced in male mice exposed to ethylene oxide by inhalation
Authors: Lewis Susan E. , Barnett Lois B. , Felton Carolyn , Johnson F. M. , Skow Loren C. , Cacheiro Nestor , Shelby Michael D.
Published: February 2007

The offspring of DBA/2J male mice exposed to ethylene oxide (EtO) by inhalation had an increased incidence of both dominant visible and electrophoretically detected mutations over that found in control populations. The progeny at risk were obtained from matings during the exposure period and were the products of germ cells that were exposed throughout the entire spermatogenic process. The results reported here suggest that male germ cells repeatedly exposed to EtO during spermatogenesis are susceptible to EtO‐induced transmissible damage.
The effect of cell passage on the susceptibility of BALB/3T3 clone A31‐1‐1 cells to 3‐methylcholanthrene‐induced morphological transformation
Authors: Sheu C. W. , Moreland F. M. , Dunkel V. C.
Published: February 2007

The response of BALB/3T3 clone A31‐1‐1 cells to chemically induced morphological transformation was evaluated using 3‐methylcholanthrene (MCA). Stock cultures were initiated from cryopreserved cells, grown in T25 flasks containing 5 ml of medium, and replated at subconfluency. Serially transferred cells were then subjected to transformation assay. After 24‐hr seeding, cells were incubated 48 hr with MCA in a 5% CO2 incubator. They were then rinsed and incubated for an additional 4 weeks with twice weekly medium change. Type III foci were scored after fixation and staining with Giemsa. With serial passage from the frozen state, cells of passages 3‐14 had a low level of spontaneous transformation; zero to 6 type III foci per 20 dishes were counted. In the MCA‐treated cultures the number of transformed foci, however, increased with passage. Such passage‐related sensitivity to MCA was demonstrated for cells cultured in two batches of sera: one from MA Bioproducts (Lot no. 2E052) and the other from Armour Pharmaceuticals (Lot no. Y65801). The passage‐related increase in number of transformed foci was not related to doubling time, cloning efficiency, or MCA‐induced growth inhibition.
Detection of mutagenic activity in the urine of rodents treated with p‐rosaniline
Authors: Lawlor Timothy E. , Haworth Steve R. , Lilja Herman S. , Cameron Thomas P. , Dunkel Virginia C.
Published: February 2007

p‐Rosaniline was fed to male and female Fischer 344 rats and B6C3F1 mice at doses of 1,000 and 2,000 ppm for male rats and 500 and 1,000 ppm for female rats and mice of both sexes. Urine was collected overnight at 1‐wk intervals over a 4‐wk treatment period and frozen until its use in the mutagenicity assay. The neat urine was tested in triplicate without S‐9 on Salmonella tester strains TA98, TA100, TA1535, and TA1537 at 0.75, 0.5, 0.2, and 0.05 ml per plate. When sufficient urine was available, samples were tested on TA100 in the presence of S‐9. Either urine samples were pretreated for 18 hr at 37°C with β‐glucuronidase, or the deconjugating enzyme was added to the top agar at the time of plating in the mutagenicity assay (non‐pretreatment). Direct‐acting mutagenic activity was detected on TA98 in the urine from male mice, but only when using the non‐pretreatment deconjugation method. No direct‐acting mutagenic activity was detected in the urine of male and female rats and female mice; however, in the presence of S‐9, mutagenic activity was observed in the urine of male rats and in the urine of male and female mice regardless of the deconjugation method used. The non‐pretreatment method was superior for detecting direct acting mutagenic activity, and the pretreatment method was superior for detecting mutagenic activity requiring metabolic activation by S‐9.
The lens and cataract: Clastogenic responses in epithelial cells of the organ‐cultured rat lens
Authors: Geard Charles R. , Worgul Basil V.
Published: February 2007

The epithelial cells of die vertebrate lens have an unique character and a probable involvement in cataract formation, which could be initiated by exogenous stimuli.

Individual rat lenses were organ‐cultured, and the effects of mitomycin C and gamma rays on sister chromatid exchanges (SCE), chromosomal aberrations, and cellular kinetics assessed in cells from the epithelial monolayer. SCE showed about a 5.5‐fold increase over the mitomycin C dose range (0, 17, 83, 170 nM), while chromosomal aberrations increased 38‐fold. In cells from untreated lenses, SCE were 1,600 times more frequent than aberrations and at a level consistent with in vivo assessments in other cell types. Gamma rays (up to 4 Gy) had a greater inhibiting effect on cellular progression, while 17 nM mitomycin C and 1 Gy induced similar clastogenic responses.

This first demonstration of such changes in lens epithelial cells expands on the cell types available for monitoring potential mutagen‐carcinogens. Additionally chromosomal changes resulting from lens cellular challenge could be the basis of later cytopathological changes in the lens, of which cataract is the primary concern to humans. Potential cataractogens warrant monitoring, and the study outlined may aid in this endeavor, as well as contributing to an understanding of cataract etiology.
Application of SOS umu‐test for the detection of genotoxic volatile chemicals and air pollutants
Authors: Ong Tong‐Man , Stewart John , Wen Yung‐Fu , Whong Wen‐Zong
Published: February 2007

The SOS umu‐test has been used for the detection of DNA‐damaging agents. In this system the plasmid pSK1002 carrying a fused gene umuC‐lacZ was introduced into Salmonella typhimurium TA1535. The SOS function induced by genotoxic agents is detected by a colorimetric measurement of β‐galactosidase activity encoded by the lacZ gene, which is regulated by the Umu operon. This system was used with modifications to study the SOS function inducibility of volatile chemicals (propylene oxide, methyl bromide, and ethylene dibromide) and air pollutants (diesel emission, welding fumes, and cigarette smoke). Tester cells were exposed directly to the test material. The enzyme activity of the treated cells was measured according to the established procedure. Results of the study showed that all chemicals and pollutants tested induced SOS function in a dose‐related manner. These results indicate that the SOS Umu‐test is potentially useful for the in situ detection of genotoxic agents in occupational settings.
Effect of mode of administration of methyl methanesulfonate and triethylenemelamine on induction of unscheduled DNA synthesis in mouse germ cells
Authors: Sheu C. W. , Sega G. A. , Owens J. G.
Published: February 2007

The effect of route of administration on induction of unscheduled DNA synthesis (UDS) in mouse germ cells in vivo was studied using two germ cell mutagens, methyl methanesulfonate (MMS) and triethylenemelamine (TEM). The chemicals were administered to male mice C3Hf × 101°F1 by IP injection or gavage using acute or 5‐day subacute regimens. After completion of dosing, methyl‐[3H]thymidine ([3H]TdR) was injected into the testes, and spermatozoa were collected 16 days later. The sperm heads were isolated, and UDS was determined by the amount of [3H]TdR incorporated. Acute administration of MMS (2‐100 mg/kg) induced a strong, dose‐related UDS response. The response was slightly higher with IP injection than with gavage. The UDS response after five daily doses of 50 mg MMS/kg was 20‐30% higher than that induced by a single IP or gavage dose. Acute administration of TEM (0.05‐4.0 mg/kg) by IP injection or gavage induced weak and variable responses. Retesting TEM using inbred C3Hf mice produced weak but exposure‐related responses with both acute IP and gavage treatments. There was a slight increase in UDS response with subacute IP injection but not with subacute gavage. Acute testicular injection of TEM produced a higher but more variable UDS response. The study showed that gavage, as well as IP injection, can be used for the administration of test chemicals and that the subacute 5‐day regimen induced a higher UDS response than the acute regimen. Furthermore, the testicular route may enhance the detection of weak UDS inducers.
Interlaboratory studies with the chinese hamster v79 cell metabolic cooperation assay to detect tumor‐promoting agents
Authors: Bohrman J. S. , Burg J. R. , Elmore E. , Gulati D. K. , Barfknecht T. R. , Niemeier R. W. , Dames B. L. , Toraason M. , Langenbach R.
Published: February 2007

Three laboratories participated in an interlaboratory study to evaluate the usefulness of the Chinese hamster V79 cell metabolic cooperation assay to predict the tumor‐promoting activity of selected chemicals. Twenty‐three chemicals of different chemical structures (phorbol esters, barbiturates, phenols, artificial sweeteners, alkanes, and peroxides) were chosen for testing based on in vivo promotion activities, as reported in the literature. Assay protocols and materials were standardized, and the chemicals were coded to facilitate unbiased evaluation. A chemical was tested only once in each laboratory, with one of the three laboratories testing only 15 out of 23 chemicals. Dunnett's test was used for statistical analysis, and differences between treated‐ and control‐cell responses were analyzed at P ≦.01. Chemicals were scored as positive (at least two concentration levels statistically different than control), equivocal (only one concentration statistically different), or negative. For 15 chemicals tested in all three laboratories, there was complete agreement among the laboratories for nine chemicals. For the 23 chemicals tested in only two laboratories, there was agreement on 16 chemicals. With the exception of the peroxides and alkanes, the metabolic cooperation data were in general agreement with in vivo data. However, an overall evaluation of the V79 cell system for predicting in vivo promotion activity was difficult because of the organ specificity of certain chemicals and/or the limited number of adequately tested nonpromoting chemicals.
Chromosomal aberrations induced by in vitro irradiation: Comparisons between human sperm and lymphocytes
Authors: Brandriff B. F. , Gordon L. A. , Ashworth L. K. , Carrano A. V.
Published: February 2007

Types and frequencies of structural aberrations in human sperm and lymphocyte chromosomes from one donor were compared after in vitro irradiation with 100, 200, and 400 rad in order to determine if cells with dramatically different chromatin configurations are similarly affected and to investigate the feasibility of using lymphocytes as surrogates for germ cells in risk estimation. Sperm chromosomes were analyzed after fusion with eggs from the golden hamster. Total frequencies of induced aberrations were similar in the two cell types. However, the relative frequencies of rejoined lesions (dicentrics), compared with unrejoined lesions (chromosome breaks and acentric fragments), were different. At the three doses tested, a constant ratio of 5 dicentrics in lymphocytes for every dicentric in sperm was induced. Conversely, for every chromosome break or acentric fragment induced in lymphocytes, 1.7 such events were induced in sperm at the three doses tested.
Mutagenic screening of marker grenade dyes by the salmonella reversion assay, l5178y/tk± mouse lymphoma assay, and in vivo sister chromatid exchange analysis in mice
Authors: Moore Martha M. , Allen James W. , Claxton Larry , Doerr Carolyn , Gwaltney Carolyn , Dutcher John S. , Kohan Michael , Lawrence B. Kay , Templeto Rh , Westbrook‐Collins Barbara
Published: February 2007

Two dyes (C.I. Solvent Yellow No. 33 and a mixture of C.I. Solvent Yellow No. 33 and C.I. Solvent Green No. 3) were tested for mutagenicity in the Salmonella reversion assay and the L5178Y/TK± mouse lymphoma assay, and also for sister chromatid exchange (SCE) induction in vivo in C57B1/6J mice. In addition, a > 99.9% pure sample of the yellow dye [2‐(2′‐quinolyl)‐1,3‐indandione] was tested with and without exogenous activation in the Salmonella reversion assay and the L5178Y/TK± mouse lymphoma assay. Neither C.I. Solvent Yellow No. 33 nor the C.I. Solvent Yellow No. 33 and Solvent Green No. 3 mixture was positive for inducing SCEs in vivo. All three dyes were tested in the standard plate incorporation test in seven Salmonella strains TA98, TA100, TA102, TA104, TA1535, TA1537, and TA1538. The dyes were negative with and without exogenous activation in TA98, TA1535, and TA1538. One test with TA1537 was positive with the > 99.9% purified yellow dye. All three dyes gave weakly positive results (less than a twofold increase) with S‐9 in TA100 and were clearly positive in TA102 and TA104 both with and without S‐9. They also induced mutation at the thymidine kinase locus in mouse.
Mutagenicity of halogenated propanes and their methylated derivatives
Authors: Ratpan Flora , Plaumann Heinz
Published: February 2007

1,2,3‐Tribromopropane, 1,2,3‐trichloropropane, and 1,2‐dibromo‐3‐chloropropane are mutagenic in strains TA1535 and TA100 of Salmonella typhimurium, but only in the presence of rat liver S9 mix. This requirement for metabolic activation was unexpected for an alkyl halide and thus suggested the metabolic formation of the 2‐keto derivatives (di‐haloacetone). The 2‐methyl derivatives of the halopropane compounds did not induce a doubling of revertants compared to controls. It was demonstrated that none of these compounds is converted into a secondary material that could be determined as structurally different by gas chromatography. These observations suggest that lack of mutagenicity of the methylated compounds is a manifestation of a steric effect.
In vivo sister chromatid exchange induced by 1,2‐dichloroethane on bone marrow cells of mice
Authors: Giri Ashok Kumar , Quehee Shane S.
Published: February 2007

In vivo sister chromatid exchange induced by 1,2‐dichloroethane (DCE) was studied in bone marrow cells of mice after acute treatment for 24 hr. With the exception of the lowest concentration (0.5 mg/kg), each treated series exhibited a statistically significant increase in SCEs when compared with the control.
Plasmid copy number and mutant frequencies in s. typhimurium ta102
Authors: Albertini Silvio , Gocke Elmar
Published: February 2007

Tetracycline and chloramphenicol increase the number of mutant colonies of strain TA102, which carries the reverting gene on die plasmid pAQ1. Determination of the plasmid content by agarose gel analysis shows that the increase of the mutant colony number is paralleled closely by an increase of die number of pAQ1 plasmids per cell, indicating mat the two compounds do not increase the frequency of mutants “per gene,” but only enhance the number of the genes at which mutations can occur. Thus, not considering die molecular processes could result in mistakenly attributing the increase in the number of mutants per plate (respective to the number of mutants per cell) to a mutagenic activity of die antibiotics.
Individual and strain differences in patterns of long‐term persistence of urethane‐induced sister chromatid exchanges (sces) in mouse lymphocytes and their relation to carcinogen susceptibility
Authors: Endo Akira , Watanabe Toshiaki
Published: February 2007

Using an improved microculture method, we investigated how the patterns of persistence of urethane‐induced SCEs in lymphocytes differ among individuals and strains of mice (the ddY and C57BL strains), and we attempted to speculate on their relationship to carcinogen susceptibility. After a single intraperitoneal (i.p.) injection of 900 mg/kg of body weight of urethane into ten female mice each for the two strains, blood samples for the SCE analysis were collected from the tail vein at ten times during the 180 posttreatment days for each individual. Immediately after the treatment, SCE values increased to about three to four times the spontaneous values in all of the animals tested and then fell gradually. (The difference from spontaneous values was statistically significant until 120 days after the treatment.) Even after 180 days, however, some “outlier” cells with exceptionally high SCEs (>20) persisted. Although there was some difference in average SCEs between the ddY and C57BL strains, the magnitude of the difference was too small to account for the difference between the strains in the incidence of urethane‐induced malignancy. Also, when autopsy data at the 200th posttreatment day were matched individually with the data of SCE values within each strain, it was difficult to predict the individual risk of the occurrence of lung adenoma or other tumors from the relative difference in SCE values.
Cytotoxic and genotoxic effects of extract of particulate emission from a gasoline‐powered engine
Authors: Hadnagy W. , Seemayer N. H.
Published: February 2007

Extract of particulate matter (EPM) from gasoline engine exhaust has been investigated for cytotoxic and genotoxic effects in the concentration range 0.16‐10 μg/ml by means of short‐term bioassays using mammalian cell culture systems. Cytotoxicity is demonstrated by a strong dose‐dependent reduction of cloning efficiency after treatment of V79 cells with EPM. Employing the dye exclusion test with erythrosin B, no considerable loss of cell viability was observed. Using the same cell system, EPM revealed a highly increased number of aberrant mitoses, whereby the occurrence of C mitoses and metaphases with chromosome clusters was especially pronounced. This effect led to mitotic arrest as shown by a highly increased mitotic index at 5 and 10 μg/ml EPM. The results indicate disturbances of the mitotic spindle in a way similar to the known spindle poison colcemid. As a consequence of spindle disturbances, EPM produced numerical chromosome alterations such as aneuploidy and polyploidy. Cytogenetic analyses using human lymphocyte cultures treated with EPM revealed a slight increase of chromosomal aberrations at 10 μg/ml and a dose‐dependent induction of sister chromatid exchanges in the range 2.5‐10 μg/ml. At least, EPM showed a dose‐dependent increase in the cell transformation assay using SV 40‐infected Syrian hamster kidney cultures. The great variety of cytotoxic and genotoxic effects found with EPM suggests a potential health hazard to human populations exposed to gasoline engine exhaust. The possible contribution to cytotoxic and genotoxic activity by organolead compounds derived from antiknock additives is discussed.
Induction of chromosome aberrations and mitotic arrest by cytomegalovirus in human cells
Authors: Abubakar Sazaly , Au William W. , Legator Marvin S. , Albrecht Thomas
Published: February 2007

Human cytomegalovirus (CMV) is potentially an effective but often overlooked genotoxic agent in humans. We report here evidence that indicates that infection by CMV can induce chromosome alterations and mitotic inhibition. The frequency of chromosome aberrations induced was dependent on the input multiplicity of infection (m.o.i.) for human lung fibroblasts (LU), but not for human peripheral blood lymphocytes (PBLs) when both cell types were infected at the GO phase of the cell cycle. The aberrations induced by CMV were mostly chromatid breaks and chromosome pulverizations that resembled prematurely condensed S‐phase chromatin. Pulverized chromosomes were not observed in LU cells infected with virus stocks that had been rendered nonlytic by UV‐irradiation at 24,000 ergs/mm2 or from infection of human lymphocytes. In LU cells infected with UV‐irradiated CMV, the frequency of aberrations induced was inversely dependent on the extent of the exposure of the CMV stock to the UV‐light. In permisive CMV infection of proliferating LU cells at 24 hr after subculture, a high percentage (> 40%) of the metaphase cells were arrested at their first metaphase and displayed severely condensed chromosomes when harvested 48 hr later. A significant increase (p < 0.05) in the chromosome aberration frequency was also observed. Our study shows that CMV infection is genotoxic to host cells. The types and extent of damage are dependent on the viral genome expression and on the cell cycle stage of the cells at the time of infection. The possible mechanisms for induction of chromosome damage by CMV are discussed.
Molecular cytogenetic characterization of TCF3 (E2A)/19p13.3 rearrangements in B‐cell precursor acute lymphoblastic leukemia
Authors: Barber Kerry E. , Harrison Christine J. , Broadfield Zoe J. , Stewart Adam R. M. , Wright Sarah L. , Martineau Mary , Strefford Jon C. , Moorman Anthony V.
Published: February 2007

The t(1;19)(q23;p13.3) is one of the most common chromosomal abnormalities in B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) and usually gives rise to the TCF3‐PBX1 fusion gene. Additional rare, and sometimes cytogenetically cryptic, translocations involving the TCF3 gene have also been described. Using a dual color split‐signal fluorescence in situ hybridization (FISH) probe, we have investigated the involvement of this gene in a series of BCP‐ALLs harboring 19p13 translocations, as well as an unselected patient cohort. The TCF3 gene was shown to be involved in the majority of cases with a cytogenetically visible t(1;19) translocation, while the remaining TCF3‐negative ALLs demonstrated breakpoint heterogeneity. Although most “other” 19p13 translocations did not produce a split‐signal FISH pattern, a novel t(13;19)(q14;p13) involving TCF3 was discovered. A prospective screen of 161 children with BCP‐ALL revealed a cryptic t(12;19)(p13;p13), another novel TCF3 rearrangement, and a series of patients with submicroscopic deletions of TCF3. These results demonstrate the utility of a split‐signal FISH strategy in confirming the involvement of the TCF3 gene in 19p13 rearrangements and in identifying novel and cryptic TCF3 translocations. In addition to its role as a fusion partner gene, we propose that TCF3 can also act as a tumor suppressor gene in BCP‐ALL. © 2007 Wiley‐Liss, Inc.
MUCOSAL MELANOMAS OF THE HEAD AND NECK
Authors: Snow G. B. , Van Esch E. P. Der , van Slooten E. A.
Published: February 2007

Mucosal melanoma of the head and neck is a rare condition. This study presents a review of 26 patients with such tumors, followed up at a minimum of 5 years. The 5‐year survival rate in this group was 38%. Recurrences with a fatal outcome, however, have been encountered up to 12 years after initial diagnosis. Primary radical surgery offers the best chance for local control. Nasal‐cavity lesions seem to be associated with a better prognosis than oral‐cavity tumors. Analysis of pathologic features by microstage measurement showed that the majority of tumors were of considerable thickness. This factor may partially explain the poor prognosis associated with mucosal melanomas in comparison to their cutaneous counterparts. Local recurrences and distant metastases were the principal causes of treatment failure. A persistent treatment policy, however, may still substantially prolong survival in such cases. Regional lymph‐node metastasis did not pose a significant problem in the management of these tumors. Recognition of the nature and significance of the appearance of oral melanosis is stressed.
Malignant melanoma of the head and neck
Authors: Storm F. Kristian , Eilber Frederick R. , Morton Donald L. , Clark Wallace H.
Published: February 2007

Sixty‐nine patients with head and neck melanoma were prospectively evaluated from 1971 to 1977. Patients presenting for initial therapy underwent wide excision of their primary tumor, and those with deeply invasive melanoma also underwent regional lymphadenectomy, whether their nodes were clinically positive or negative. The results suggest that the prognosis of this tumor is similar to that of melanoma arising at other sites. Clinical stage and primary‐tumor histopathologic microstage both correlated with disease recurrence. At 1 to 75 months, patients with clinical Stage I disease had a 13% recurrence rate, while 58% of those with Stage II disease developed recurrence. Patients with superficially invasive melanoma had a 10% recurrence rate, while 17%–33% of those with deeply invasive disease developed recurrence. However, the presence of node metastases, rather than the microstage of the primary tumor, appeared to be the dominant indicator of outcome. Radical excision of the primary tumor may reduce the incidence of local disease recurrence. We believe that regional lymphadenectomy is indicated for deeply invasive melanoma.
Reinnervation of the paralyzed larynx: A review
Authors: Tucker Harvey M.
Published: February 2007

Our high‐speed and increasingly aggressive society, coupled with a continuing rise in necessary surgery of the neck and adjacent areas, accounts for the current increase in patients afflicted with vocal‐cord paralysis. Such patients may sustain relatively little persistent loss of function (e.g., when only one cord is involved, which then regains function or becomes compensated) or considerable loss (as in cases of bilateral vocal‐cord paralysis). To improve on existing methods of dealing with these problems, the author has developed and refined the nerve‐muscle‐pedicle technique for reinnervating paralyzed muscles. A nerve‐muscle pedicle obtained from the ansa hypoglossi branch to the omohyoid muscle or another strap muscle can be used to selectively reinnervate the posterior cricoarytenoid muscle in cases of bilateral‐cord paralysis, or for selective reinnervation of the lateral thyroarytenoid muscle in cases of unilateral‐cord paralysis. The bilateral reinnervation technique showed a 90% success rate in 90 patients, as demonstrated by their ability to sustain reasonable day‐to‐day activity without needing a tracheotomy tube and without manifesting further loss of voice. The unilateral technique has yielded promising results in a limited number of carefully selected patients.
Jaw cysts: Diagnosis and treatment
Authors: Summers Gordon W.
Published: February 2007

The classification, embryology, histopathology, clinical features, and treatment of benign jaw cysts are presented. Emphasis is placed on the differentiation of benign cysts from malignant radiolucent lesions of the jaws. Preservation of adjacent teeth and other vital structures is of paramount importance in the management of jaw cysts.
Nutritional concepts in the treatment of head and neck malignancies
Authors: Copeland Edward M. , Daly John M. , Dudrick Stanley J.
Published: February 2007

Cancer cachexia should no longer be a contraindication to adequate antineoplastic treatment. Current methods of nutritional assessment allow one to identify malnutrition and to follow the nutritional status of the patient throughout the cancer‐management program. Enteral nutritional repletion and maintenance remain the ideal course of action, but the gastrointestinal tract is not always readily available or advisable for use; in such circumstances, intravenous hyperalimentation (IVH) may be indicated. The properly nourished patient better tolerates cancer therapy, experiences fewer complications of malnutrition (e.g., sepsis and poor wound healing), and has a better‐functioning immune system than does his malnourished counterpart. This article reviews methods of nutritional assessment, delineates indications and techniques for nutritional repletion, and summarizes the results obtained.
Computed tomography of the normal larynx
Authors: Friedman William H. , Archer Carol R. , Yeager Vernon L. , Donovan Thomas J.
Published: February 2007

A computed tomographic analysis of normal laryngeal anatomy was undertaken using cadaver larynxes. This was part of a larger project in which patients with laryngeal carcinoma were routinely evaluated in the computed tomographic (CT) body scanner. The appearance of normal laryngeal anatomy had to be delineated before disease processes of the larynx were evaluated, and this was accomplished using a computed tomographic technique with 5‐mm slice thicknesses and a 3‐mm overlap. The scan slices were then compared with anatomic sections taken at the same levels. The comparisons demonstrate an ideal level of accuracy that can be approached in the in‐vivo larynx only with use of the latest‐generation scanners. However, CT scanning is of immediate usefulness in the diagnosis of laryngeal pathology.
The role of irradiation in the management of squamous‐cell carcinomas of the mouth and throat
Authors: Fletcher Gilbert H.
Published: February 2007

Fundamental precepts of radiation biology are presented to provide a basis for the comprehension of radiotherapy. These precepts include cell viability, randomness of cell killing by irradiation, the influence of molecular oxygen on radiosensitivity, phases of the cell cycle, and repopulation. The combined‐treatment concept is developed, and preoperative and postoperative irradiation options, as well as the optimal extent of the surgical procedure, are discussed. These principles of combined treatment are first applied to the management of neck disease, which is a common denominator to all sites. The anatomic sites of the mouth and throat are then discussed. The capabilities of radiotherapy have greatly altered treatment planning for carcinomas of the mouth and throat; one must now develop an initial overall plan that varies with the extent and anatomic site of the primary lesion, the extent of neck disease, and the probability of spread to clinically uninvolved lymphatic areas.
Microsurgery: A technical discussion for head and neck surgeons
Authors: Lee Sun , Orloff Marshall J.
Published: February 2007

Despite mechanical and technical advances that have been made in fields allied with microsurgery, Carrell and Guthrie's basic concept of small‐blood‐vessel anastomosis has not changed significantly. However, with refined, finer sutures and needles as well as improved jewelers' and ophthalmic surgical instruments, individuals can now readily practice under high magnification. With repeated practice using rats, the operator can successfully manage finer structures, such as blood vessels less than 1 mm in diameter. Head and neck surgeons have an advantage in this area because of their extensive experience and skill in manipulating operating microscopes.
Soft‐palate reconstruction with the modified pharyngeal flap
Authors: Sofferman Robert A.
Published: February 2007

Soft‐palate malignancies classically have been managed with radiation therapy as the principal therapeutic modality. The survival rates are poor and may indicate the need for an aggressive combined approach using wide surgical resection. The use of surgery as the definitive control measure, however, raises objections about the loss of velopharyngeal closure in phonation and deglutition. The functional consequences of palate resection can be reversed with a one‐ or two‐stage modified pharyngeal flap procedure. The surgical techniques and three representative cases are presented.
Sialotorrhea: A manifestation of first‐branchial‐cleft anomaly?
Authors: Cremers C. W. R. J. , Manni J. J. , Wes B. J. , Van Den Broek P.
Published: February 2007

A 16‐year‐old‐girl had a six‐month history of sialotorrhea. Lipiodol sialography of the right parotid revealed overflow of Lipiodol into the right external acoustic meatus. Surgical exploration that left the facial nerve intact disclosed a branchiogenic anomaly confirmed at histologic examination—a lesion that extended parallel to the external acoustic meatus—and aplasia of the pars tympanica of the right petrosal bone. It is concluded that the branchiogenic anomaly is a first‐branchial‐cleft anomaly (type I according to Work); the aplasia of the pars tympanica ossis temporalis remains unexplained. The sialotorrhea probably resulted from an infection of the branchiogenic cyst.
Mandible stabilization between ablative and reconstructive surgery
Authors: Leeb Dianne C. , Friedlander Arthur H. , Mazzarella Lawrence
Published: February 2007

The biphase external skeletal‐fixation splint (Morris splint) for mandibular stabilization has been used in cases of ablative surgery. It is a practical approach to stabilization for patients whether or not they undergo reconstruction, either immediate or delayed. The Morris splint can be applied without increasing the time required for major resection. It can be left in place for prolonged periods, but it still allows easy surgical access and easy postoperative care and observation. While not a new tool, it has been little used by the head and neck cancer surgeon, probably because it has not been presented for this purpose but rather for treating fractures. A practical approach to the use of the Morris biphase splint is presented, as well as the indications for its use and some results of our experience with this tool.
Carcinoma in a Zenker's diverticulum
Authors: Donald Paul J. , Huffman David I.
Published: February 2007

Zenker's diverticulum is a common developmental anomaly seen usually in the elderly. Carcinoma in this pharyngoesophageal outpouching has been reported in only 23 instances. A 55‐year‐old woman is presented whose only symptoms were dysphagia and periodic regurgitation of bloodstained material. Barium swallow and esophagoscopy confirmed the presence of a neoplasm, and biopsy revealed an epidermoid carcinoma. Wide field resection was followed by a full course of irradiation and secondary pharyngoesophageal reconstruction. The patient was free of disease at three‐year follow‐up.
Treatment of radiation‐induced alopecia
Authors: Jacobs Joseph B. , Monell Charles
Published: February 2007

Radiotherapy is frequently employed in the management of head and neck neoplasia, either as an adjunct to surgery or as the sole treatment modality. Consequently, radiation alopecia—a well‐known complication of high‐dosage radiotherapy—is seen often. Longer patient survival, especially with earlier discovery of the malignancy and more refined treatment regimens, will provide the surgeon with the opportunity to treat radiation alopecia by means of the punch graft technique of hair transplantation. The technique is substantially similar to that employed in treating male pattern baldness, although the approach to the recipient and donor areas must be modified. A successful case report is documented and a modified approach is highlighted.
Deliberate hypotension in head and neck surgery
Authors: Ward C. F. , Alfery David D. , Saidman L. J. , Waldman J.
Published: February 2007

The deliberate reduction of blood pressure in an attempt to reduce intraoperative blood loss has generated significant controversy in the 30 years since its clinical introduction. Numerous series have been reported, but few have met generally accepted, current criteria for controlled studies. In this article, the effect of blood pressure reduction on organ perfusion will be presented together with a review of techniques of achieving hypotension. A summary of results is included and, based on this data, recommendations are offered regarding the application and limits of deliberate hypotension.
Radiology of congenital deformities of the ear
Authors: Hanafee William N. , Bergstrom La Vonne
Published: February 2007

By depicting the status of the middle ear beyond atretic canals, multidirectional tomography can materially assist in the planning of surgery for conductive hearing losses. The course of the facial nerve is best demonstrated by the Guillen projection and by lateral projections. Deformities of the inner ear structures may be surveyed by similar projections. The base view accurately predicts the status of the cochlea. If lesions are classified as external canal deformities, middle ear deformities, or inner ear deformities, the clinician may more easily identify hereditary versus environmental syndromes.
The vestibular aqueduct—Tomographic evaluation in Meniere's disease—A preliminary report
Authors: Sackett Joseph F. , Strother Charles M. , Arenberg I. Kaufman , Goldman George
Published: February 2007

Frontal and off‐lateral complex motion tomography was performed in 72 consecutive patients selected for endolymphatic sac surgery for episodic vertigo or sensorineural hearing loss. They were selected for this operation because of a fluctuating hearing loss. The morphology and visualization of the vestibular aqueduct and the degree of periaqueductal pneumatization were correlated with surgical results and the presence of bilateral disease. The surgical results were evaluated with use of the classification of the American Academy of Ophthalmology and Otolaryngology. Computer analysis was performed on the data for vestibular aqueduct radiographic anatomy and surgical results or bilateral disease. There was no correlation between visualization or morphology of the vestibular aqueduct and surgical results or presence of bilateral disease.