ISSN:0893-6692    

DOI:10.1002/em.2850110202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractChinese hamster ovary (CHO) cells were exposed to 2‐acetylaminofluorene (2‐AAF) and 2‐aminofluorene (2‐AF), and several of theirN‐oxidized metabolites in order to study the mechanisms by which arylamides and arylamines produce mutations in mammalian cells. The number of mutations induced at the hypoxanthine‐guanine phosphoribosyl transferase locus by each compound (mutants/106CHO cells/nmol compound/ml) was estimated to be:N‐acetoxy‐2‐AAF, 310;N‐hydroxy‐2‐AF, 3;N‐hydroxy‐2‐AAF (with and without hepatic S9 activation), 0.7; 2‐AAF (with S9), 0.1; and 2‐AF (with S9), 0.09. With each compound, DNA adducts were also identified and quantified, and in all cases the major adduct wasN‐(deoxyguanosin‐8‐yl)‐2‐AF. 2‐AAF andN‐hydroxy‐2‐AAF also formed minor amounts ofN(deoxyguanosin‐8‐yl)‐2‐AAF and 3‐(deoxyguanosin‐N2‐yl)‐2‐AAF. The relationship between mutation induction and adduct formation for each of the derivatives was similar to that previously reported forN‐hydroxy‐2‐AF. Inclusion of the deacetylase inhibitor, paraoxon, reduced the mutagenicity of 2‐AAF,N‐hydroxy‐2‐AAF andN‐acetoxy‐2‐AAF, and the DNA adducts produced byN‐acetoxy‐2‐AAF to background levels. Acetyl coenzyme A increased the mutations and CHO cytosol‐mediated DNA binding ofN‐hydroxy‐2‐AAF, but did not substantially increase these responses fromN‐hydroxy‐2‐AF.N‐Hydroxy‐2‐AAF was not detectably metabolized by CHO cells. Taken together, these data indicate that CHO cells metabolizedN‐acetoxy‐2‐AAF to a reactive derivative byN‐deacetylation toN‐acetoxy‐2‐AF, whileN‐hydroxy‐2‐AF reacted direcitly with DNA. The major pathway ofN‐hydroxy‐2‐AAF activation appeared to be an initialO‐acetylation toN‐acetoxy‐2‐AAF and this occurred to only a limited extent in the CHO cells.N‐Hydroxy‐2‐AAF also seemed to form an additional unknown ester intermediate that gave rise to acetylated DNA adducts. The l

ISSN:0893-6692    

DOI:10.1002/em.2850110203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe capacity of lesions induced by gamma radiation to produce sister chromatid exchanges (SCE) in successive divisions in mouse bone marrow cells in vivo was evaluated using a protocol for the three‐way differentiation of sister chromatids.Evidence was obtained that exposure to gamma radiation induces DNA lesions that result in the formation of SCE at the same locus in two successive cell divisions. The relevance of this observation with respect to DNA repair and mutagenesis is discusse

ISSN:0893-6692    

DOI:10.1002/em.2850110204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractNine coffee preparations, four caffeinated instant brands, three caffeinated drip coffees, and two decaffeinated coffees, one of which was an instant brand, were evaluated for mutagenicity by the Ames assay usingSalmonella typhimuriumTA100, TA102, and TA104. All the coffees contained direct‐acting mutagens, which reverted the three strains. The inclusion of a rat microsomal enzyme preparation reduced the mutagenic response of the three strains in the presence of some of the coffee samples. Both glyoxal and methylglyoxal, 1,2‐dicarbonyls found in the coffees were mutagenic. The concentration of glyoxal, methylglyoxal, diacetyl, and guiacol were measured by gas chromatography/mass spectrometry. Caffeine, furfural, and 5‐methylfurfural concentrations were determined by high performance liquid chromatography. Although lower concentrations of methyglyoxal were found in the drip caffeinated coffees, the mutagenic potency of these preparations was higher than the instant coffees on a weight basis especially when TA104 was the indicator organism. Our findings agree with those of other workers who have shown that carbonyl compounds, which were present in all the brands tested, are partially responsible for the mutagenic response of coffee but that additional mutagens are also pr

ISSN:0893-6692    

DOI:10.1002/em.2850110205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractCalcium cyclamate, an artificial sweetener, was studied for its effectiveness in inducing transmissible chromosomal aberrations in germ cells of male mice. Both the dominant‐lethal and the heritable translocation tests were carried out following daily treatment (on weekdays) of males by oral intubation with the maximum tolerated dose for 6 weeks. Calcium cyclamate is negative in both tests; therefore, there is no evidence of induced chromosome breakage and exchang

ISSN:0893-6692    

DOI:10.1002/em.2850110206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractTo determine the positive and negative classification error rates associated with the HTA in our laboratory, F1sons of TEM‐exposed CD‐1 male mice were evaluated by the sequential fertility method with subsequent cytogenetic analysis. Males who sired three litters of size 10 or less when mated to primiparous females from either the B6C3F1or the BCF1strain were classified as partial steriles. When meiotic chromosome analyses revealed the presence of at least two cells containing multivalent figures, males were classified as translocation heterozygotes. When the fertility evaluation and the cytogenetic analysis were compared, normal fertility was observed on 5 of 83 (6.02 %) translocation‐bearing F1males mated to B6C3F1tester females and on 3 of 83 (3.61 %) F1males mated to BCF1tester females. Thus, the false‐negative error rates were 6.02% and 3.61% with these two tester strains. Multivalent figures were not observed in the meiotic chromosomes of 410 F1males. Of these, 12 (2.93%) had reduced fertility when mated to the B6C3F1tester strain as did 7 (1.71%) mated to the BCF1strain. Thus, the false‐positive error rates with these two tester strains were 2.93% for the B6C3F1strain and 1.71 % for the BCF1strain. Our results indicate that nonzero error rates, both false‐positive and false‐negative, are associated with the sequential mating method HTA. In addition, the magnitude of these error rates was influenced not only by the tester female strain but also by the genotype

ISSN:0893-6692    

DOI:10.1002/em.2850110207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractOne of the mutagenic byproducts associated with chlorinated humic waters and kraft pulp bleaching effluents was recently identified as 3‐chloro‐4‐(dichloromthyl)‐5‐hydroxy‐2(5H)‐furanone. This compound and several related chlorofuranones and precursors were synthesized and evaluated for direct‐acting mutagenicity inSalmonella typhimuriumtester strain TA100. Mutagenicity was greatest for 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5H)‐furanone, its 5‐methoxy derivative, and the precursor in their synthesis, 3‐(dichloromethyl)‐2,4,4‐trichloro‐2‐butenoic acid. Several of the compounds were tested in the presence of added rat liver homogenate S9 fraction, and in all cases mutagenicity was substantially reduced. An important structural feature which may govern the mutagenic response in these instances appears to be thecisarrangement of CHCl2and Cl substituents on a carbon‐carbon double bond. These compounds may also be transformed in vitro to the same acyclic chlorine substituted alpha, beta‐unsaturated aldehyde derivative, which is proposed to be the ag

ISSN:0893-6692    

DOI:10.1002/em.2850110208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractTritiated thymidine (3HTdR; 120 μCi/mouse) increases the incidence of micronucleated polychromatic erythrocytes (MPE) in bone marrow PE of both B6CF1 and CBA male mice. This effect observed in vivo reflects the clastogenicity reported by other investigators for3HTdR in vitro. Thymidine itself was concluded to be inactive in the assay at a dose‐level 100 times greater than that required to show activity for3HTdR. These observations are of relevance to those employing3HTdR to monitor the mitogenic activity and the genotoxicity of chemica

ISSN:0893-6692    

DOI:10.1002/em.2850110209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractTreatment of cells with low levels of alkylating agents for extended periods of time causes them to become resistant to the lethal and mutagenic effects of subsequent high‐level challenge treatments with alkylating agents. This increased resistance has been called the adaptive response to alkylation damage and results from the induction of an alkylation‐specific DNA repair response. The adaptive response is most efficiently induced by methylating agents and is most effective against the lethal and mutagenic effects of methylation damage to DNA. Four genes have been identified as components of this response,ada, alkA, alkB and aidB.The functions of two of these genes are known. AlkA protein functions as a glycosylase that repairs N3‐meA, N3‐meG, O2‐meT, and O2‐meC residues in DNA, and Ada protein functions as an alkyltransferase that removes alkyl groups from O6‐meG, O4‐meT residues as well as methylphosphotriesters. After it interacts with methylated DNA, Ada protein functions as a positive regulatory element that controls the expression of the adaptive response by stimulating the expression of theada‐alkBoperon, and thea

ISSN:0893-6692    

DOI:10.1002/em.2850110210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0893-6692    

DOI:10.1002/em.2850110211

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY