ISSN:0270-3211    

DOI:10.1002/tcm.1770100302

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe objectives, applications and limitations of laboratory methods for assessing human exposure to carcinogens are concisely discussed. The available technologies include cytological, cytogenetic and molecular analyses, somatic cell mutation, carcinogen‐DNA or carcinogen‐protein adducts, metabolic markers, and chemical or biological analyses of expired air, body fluids, and excr

ISSN:0270-3211    

DOI:10.1002/tcm.1770100303

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

年代:1990

数据来源: WILEY

摘要:

AbstractCytogenetic endpoints, conventionally chromosomal aberrations, and later sister chromatid exchanges and micronuclei have long been used to assess exposure of human populations to genotoxic agents. Although the adverse nature of somatic chromosome damage is recognized at the group level, no ill‐health manifestations have been causally related to cytogenetic damage at the individual level. In work‐related exposures, e.g., ethylene oxide, styrene, benzene, vinyl chloride, and alkylating anticancer agents have been shown to induce somatic chromosomal damage in several studies. For all of these, a carcinogenic risk to humans has also been documented.The possible association of somatic chromosome damage and cancer will be elucidated in a Nordic prospective study. The objective is to find out the significance of a high or low score in any of the cytogenetic parametres to risk of cancer. In the Finnish part of the cohort of 806 individuals, 10 cases of cancer were observed during the first follow‐up period. Although the cohort is young and the numbers small, a slightly significant (P= 0.04) trend was observed for individuals with cancer and a score of chromosomal aberrations. No trend was observed for sister chromatid exchanges.The application of cytogenetic surveillance is still not routine methodology, but it is useful and informative in carefully controlled study designs. Special efforts should be directed toward combining different disciplines, i.e., cytogenetics, adduct monitoring, and end‐effect epidemiology, in order to reach quantitativeness in risk ass

ISSN:0270-3211    

DOI:10.1002/tcm.1770100304

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe32P‐postlabeling technique introduced by Randerath and co‐workers has been particularly successful with stable and nonpolar DNA adducts, but the assay has not been used to any large extent to detect 7‐alkylguanine derivatives. In the present communication, we have investigated the phosphorylation reaction by T4polynucleotide kinase using 7‐methyl‐3′‐dGMP, ring‐opened 7‐methyl‐3′‐dGMP and enzyme‐digested methylated DNA as substrates.The methylated substrates were detected at femtomol (fmol) sensitivities. 7‐methyl‐3′‐dGMP was quantitatively phosphorylated at these low concentrations. The efficiency of phosphorylation of the ring‐opened product was less. It was shown that ring‐opened 7‐methyl‐3′‐dGMP was resistant to digestion with nuclease P1, making alkali‐treatment and enzyme digestion of DNA possible approaches

ISSN:0270-3211    

DOI:10.1002/tcm.1770100305

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe use of biochemical markers may improve the potentialities of etiologic epidemiology. Exposure markers or markers of biologically effective dose allow better exposure assessment, therefore decreasing misclassification in epidemiological studies. Markers of individual susceptibility (such as metabolic polymorphism) permit the identification of subgroups of subjects at higher risk of cancer. In general, the integration of biochemical methods and an epidemiological design is helpful in the study of the sources of interindividual variability in response to carcinogenic stimuli. We review several investigations making use of biochemical measurements in the field of cigarette‐induced bladder cance

ISSN:0270-3211    

DOI:10.1002/tcm.1770100306

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe 18 posters, grouped under mutagenicity testing, metabolic activation, mechanisms of mutation and chromosome damage, human monitoring and safety are critically discussed. It is pointed out that rather than applying a single test, a battery of well‐validated in vitro and in vivo tests is required. As a testing strategy, the one developed by Ashby (2) is briefly mentioned. The value of the Salmonella assay and of in vitro cytogenetics as short term tests for detecting carcinogens, and of the bone marrow micronucleus test as one for assessing germ cell mutagenesis is pointed out. Various assays now available for measuring gene mutations in human lymphocytes and erythrocytes are briefly described. Since we have a considerable data‐base for germ cell mutations in the mouse and data are now being collected for mutations in human somatic cells, the importance of studies on mutation induction in somatic cells of the mouse is emphasized. Such data on mouse somatic cells will help to define with greater precision mutation induction to be expected in human germ cells; that is genetic risks in humans on the basis of a “parallelogram‐like” extrapolation using somatic mutations in man and germ cell mutations in the mouse can now be c

ISSN:0270-3211    

DOI:10.1002/tcm.1770100307

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

年代:1990

数据来源: WILEY

摘要:

Abstract1, 2, 3, 4‐Tetrahydro‐7, 12‐dimethylbenz(a)anthracene (TH‐DMBA), its six possible fluoro‐substituted regioisomers, and the C‐7 exo methylene tautomer of the 11F derivative have been investigated for their cytotoxicity and for their ability to induce anchorage‐independent growth and to form adducts in human neonatal foreskin fibroblasts. All compounds tested exhibited a low level of cytotoxicity, determined as percent cloning efficiency, up to a final concentration of 30 μ/ml. Except for 5F‐TH‐DMBA and the C‐7 exo methylene tautomer, all compounds induced anchorage‐independent growth of neonatal foreskin fibroblasts in soft agar at all concentrations tested (1, 3, 10, and 30 μ/ml). The C‐7 exo methylene tautomer induced anchorage‐independent growth only at a concentration of 10 μ/ml. Among the compounds tested the 6F derivative was the most effective compound at 1 μ/ml. The D‐ring fluoro isomers induced anchorage‐independent growth at a frequency comparable to TH‐DMBA itself, with the 11F derivative being the least effective of the four D‐ring regioisomers. All compounds except 5F‐TH‐DMBA formed detectable adducts with cellular DNA as determined by32P postlabeling procedures, when the cells were treated at 1 μ/ml. Two adducts were detected in cells treated with TH‐DMBA and four adducts were detected in DNA obtained from cells treated with 6F‐TH‐DMBA. The level of bonding for the D‐ring fluoro isomers was quantitatively less and sometimes qualitatively different than that for TH‐DMBA. For the D‐ring compounds, the ability to induce anchorage‐independent growth frequency correlated with the total quantity of adduct formed. The C‐7 exo methylene tautomer formed a single adduct and the level of bonding was less than one adduct per 109nucleotides. Analysis of these results led to the proposal that the planar anthracene ring structure (rings B, C, and D) of TH‐DMBA and possibly oxidative metabolism at benzylic carbon 4 of the A‐ring are important to DNA bond

ISSN:0270-3211    

DOI:10.1002/tcm.1770100308

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

年代:1990

数据来源: WILEY

摘要:

AbstractMutagenicity and carcinogenicity of metronidazole (MT) are imputable to the formation of toxic intermediates, which include radical forms derived from the nitroreductive process. Since dimethylsulfoxide (DMSO) the “universal” solvent, can quench free radicals in vitro, it was suggested that DMSO might protect by scavenging free radical generation in vivo. This study wanted to evaluate if DMSO (given concomitantly or prophylactically) protects against the organospecific mutagenicity of MT in vivo by means of the intrasanguineous host‐mediated assay. DMSO used as solvent showed a 20%–30% reduction in the mutation frequencies by MT. Prophylactic administration of DMSO for 3 d caused a suppression of the organospecific mutagenicity. However, some increases in the spontaneous mutation frequency and enhancement of MT mutagenicity in kidney were observed. The protective effect was paralleled by a decrease in NADPH cytochrome c (P450) reductase in liver, kidney, and to a lesser extent in lung microsomes from pretreated mice. Inhibition of mutagenic activity might be related to scavenging of radical species as supported by the lack of tissue specificity and no appreciable changes in specific enzyme activity. However, changes in reductase content in prophylactically pretreated mice can affect the quantitative biotransformation of MT to the proximal mutagen contributing to the observed suppression in mutation freq

ISSN:0270-3211    

DOI:10.1002/tcm.1770100309

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

年代:1990

数据来源: WILEY

摘要:

AbstractStudies were performed to determine the genotoxic effect of cytochalasin‐B (CYB) and to compare the efficacy of the cytokinesis‐blocked binucleated cells (CB) for scoring micronuclei (MN) with the conventional mononuclear method, following treatment with mitomycin C and cyclophosphamide. The results show that 3–4 μg/ml of CYB induced maximum number of binucleated cells without any genotoxic effect and the frequency of MN in binucleated cells was higher than that in the mononucleated cells (P<0.05) but less than twofold. However, MN frequencies in binucleated cells were not equivalent to the frequencies of mononucleated cells, since MN in binucleated cells represent two nuclei. These results suggest that further study is required to consider CB method as a more reliable approach for scor

ISSN:0270-3211    

DOI:10.1002/tcm.1770100310

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

年代:1990

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770100301

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

年代:1990

数据来源: WILEY