bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractPreviously 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

AbstractDi‐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

AbstractWe 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

AbstractThe 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

AbstractThe 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

Abstractp‐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

AbstractThe 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

AbstractThe 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

AbstractThe 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

AbstractThree 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

AbstractTypes 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

AbstractTwo 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

Abstract1,2,3‐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

AbstractIn 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

AbstractTetracycline 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

AbstractUsing 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.