A further assessment of factors influencing measurements of thioguanine-resistant mutant frequency in circulating T-lymphocytes

Cole, Jane; Green, Michael H.L.; James, Stuart; Henderson, L.M.; Cole, H.S.D.

doi:10.1016/0165-1218(88)90044-4

Cited by 137 publications

(39 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It will be interesting to study whether subjects who sustain high exposure to benzo[a]pyrene and other (PAHs) show any significant increase of base substitution (e.g., GC>TA transversion mutation) or other type of mutation as compared to unexposed controls. Such studies could focus on heavy smokers who are known to have increased frequencies of in vivo HPRT mutation (8,9) and on coke oven workers preferentially having concomitant exposure evaluation by measurements of individual PAH-DNA adduct levels (38).…”

Section: Discussionmentioning

confidence: 99%

“…Human T-cell cloning can be performed with high cloning efficiency, and selection for HPRT mutants in mediums containing 6-thioguanine yields reliable and reproducible estimates of the mutation frequency in the T-cell population from the peripheral blood of individual subjects (5)(6)(7)(8)(9). Information with regard to the clonality and origin of HPRT mutation is obtained by molecular analysis of the clonespecific T-cell receptor rearrangement (10).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mutations induced in the hypoxanthine phosphoribosyl transferase gene by three urban air pollutants: acetaldehyde, benzo[a]pyrene diolepoxide, and ethylene oxide.

Lambert

Andersson

Bastlová

et al. 1994

Environ Health Perspect

View full text Add to dashboard Cite

Provisional mutational spectra at the hypoxanthine phosphoribosyl transferase (HPRT) locus in vitro have been worked out for acetaldehyde (AA) and benzo[alpyrene diolepoxide (BPDE) in human (T)-lymphocytes and for ethylene oxide (EtO) in human diploid fibroblasts using Southern blotting and polymerase chain reaction (PCR)-based DNA sequencing techniques. The results indicate that large genomic deletions are the predominating hprt mutations caused by AA and EO, whereas BPDE induces point mutations that are mainly GC>TA transversions. The mutational spectra induced by the three agents are clearly different from the background spectrum in human T-cells. Thus, the hprt locus is a useful target for the study of chemical-specific mutational events that may help identify causes of background mutation in human cells in vivo. -Environ Health Perspect 102(Suppl 4): 135-138 (1994).

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mutations induced in the hypoxanthine phosphoribosyl transferase gene by three urban air pollutants: acetaldehyde, benzo[a]pyrene diolepoxide, and ethylene oxide.

Lambert

Andersson

Bastlová

et al. 1994

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…In addition to the mutant frequency, the age, sex, smoking status, nonselective cloning efficiency, number of cells plated for mutant selection, and the total number of mutants are presented. Although our database is small, it does appear that, as has been shown by other laboratories (13,14), there is an age-dependent increase in the mean mutant frequency (Fig. 2).…”

Section: Resultsmentioning

confidence: 81%

Quantification and molecular characterization of hprt mutants of human T-lymphocytes.

Moore

Harrington‐Brock

Zimmerman

et al. 1993

Environ Health Perspect

View full text Add to dashboard Cite

Somatic mutations have been implicated as critical early events in carcinogenesis. Point mutations, deletions, and translocation events have been shown to activate oncogenes or inactivate suppressor oncogenes. In human population monitoring, quantitative analysis of mutation events that affect gene function is limited to those genes whose cellular phenotypes can be identified by selection procedures and to those tissues (like blood) that are accessible for analysis. In an effort to determine the frequency and types of mutations that can be detected at the hypoxanthine guanine phosphoribosyltransferase (hprt) gene, we have used the T-cell cloning assay and have developed a strategy to propagate mutants and screen for point mutations and breakage events. Early in the clonal expansion of mutants, 1-2 x 10(4) cells are prepared as a crude cell lysate, and a sample is analyzed using the multiplex polymerase chain reaction (PCR). Those mutants that yield altered DNA fragments are then expanded for Southern blot hybridization, PCR, flanking probe isolation, and DNA sequencing. To date we have found presumed point mutations, intragenic deletions, and deletions that extend outside of the hprt gene. By analyzing mutations in selectable, nonessential gene markers, it should be possible to understand mechanisms of both spontaneous and induced genetic damage. An association of these specific genetic events with human diseases and the evaluation of the ability of environmental chemicals to induce these specific types of mutations will lead to a rational basis for evaluating risks from various chemical exposures. Images FIGURE 3.

show abstract

“…Although, strictly speaking, smoking is a mutagen exposure, it is so ubiquitous that it must be accounted for in human population monitoring. An increase in variant/mutant frequency with age has been found for all assays tested (9,(25)(26)(27)(28)(29)(30)(31). Smoking has been found to increase mean gpa variant and hprt variant and mutant frequency values (25,28,(31)(32)(33).…”

Section: Somatic Mutations In T-lymphocytesmentioning

confidence: 99%

Somatic Cell Gene Mutations in Humans: Biomarkers for Genotoxicity

Albertini¹,

Nicklas²,

O'Neill³

1993

Environmental Health Perspectives

View full text Add to dashboard Cite

A further assessment of factors influencing measurements of thioguanine-resistant mutant frequency in circulating T-lymphocytes

Cited by 137 publications

References 29 publications

Mutations induced in the hypoxanthine phosphoribosyl transferase gene by three urban air pollutants: acetaldehyde, benzo[a]pyrene diolepoxide, and ethylene oxide.

Mutations induced in the hypoxanthine phosphoribosyl transferase gene by three urban air pollutants: acetaldehyde, benzo[a]pyrene diolepoxide, and ethylene oxide.

Quantification and molecular characterization of hprt mutants of human T-lymphocytes.

Somatic Cell Gene Mutations in Humans: Biomarkers for Genotoxicity

Contact Info

Product

Resources

About