Are chromosome aberrations in circulating lymphocytes predictive of future cancer onset in humans? Preliminary results of an Italian cohort study

Bonassi, Stefano; Abbondandolo, Angelo; Camurri, Lamberto; Prá, Leda Dal; Ferrari, Marcella De; Degrassi, Francesca; Forni, Alessandra; Lamberti, Laura; Lando, Cecilia; Padovani, P; Sbrana, Isabella; Vecchio, Daniela; Puntoni, Riccardo

doi:10.1016/0165-4608(94)00131-t

Cited by 284 publications

(130 citation statements)

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“…One of these test systems is CA which has been considered as an early warning signal for cancer development (Bonassi et al 1995;Hagmar et al 1998). SCE represent the interchange of DNA replication products at apparently homologous loci.…”

Section: Discussionmentioning

confidence: 99%

The in vitro genotoxicity of benzoic acid in human peripheral blood lymphocytes

2009

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The chromosomal aberration (CA), sister chromatid exchange (SCE) and micronucleus test (MN) were employed to investigate the in vitro effect of antimicrobial food additive benzoic acid on human chromosomes. Lymphocytes were incubated with various concentrations (50, 100, 200 and 500 lg/ mL) of benzoic acid. The results of used assays showed that benzoic acid significantly increased the chromosomal aberration, sister chromatid exchange and micronucleus frequency (200 and 500 lg/mL) without changing the pH of the medium in a dosedependent manner. Also this additive significantly decreased the mitotic index (MI) at the highest concentration for 24 h and 100, 200 and 500 lg/mL for 48 h. This decrease was dose-dependent as well. However, it did not effect the replication (RI) and nuclear division (NDI) indices.

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Section: Discussionmentioning

confidence: 99%

The in vitro genotoxicity of benzoic acid in human peripheral blood lymphocytes

2009

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“…Epidemiological evidence supports a predictive value of an elevated frequency of chromosomal aberrations in peripheral blood lymphocytes (Hagmar et al, 2004). In the Nordic (Hagmar et al, 1994), Italian (Bonassi et al, 1995), and Czech (Smerhovsky et al, 2001), cohort studies, the authors evaluated the association between the frequency of chromosomal aberrations, sister chromatid exchange or micronuclei in peripheral blood lymphocytes of individuals and the subsequent risk of cancer. The reported findings showed an approximately two-fold increase in the risk of cancer among those with the highest frequencies of chromosomal aberrations (reviewed in Hagmar et al (2004)).…”

Section: Discussionmentioning

confidence: 99%

DNA repair capacity as a possible biomarker of breast cancer risk in female BRCA1 mutation carriers

et al. 2007

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The BRCA1 gene product helps to maintain genomic integrity through its participation in the cellular response to DNA damage: specifically, the repair of double-stranded DNA breaks. An impaired cellular response to DNA damage is a plausible mechanism whereby BRCA1 mutation carriers are at increased risk of breast cancer. Hence, an individual's capacity to repair DNA may serve as a useful biomarker of breast cancer risk. The overall aim of the current study was to identify a biomarker of DNA repair capacity that could distinguish between BRCA1 mutation carriers and non-carriers. DNA repair capacity was assessed using three validated assays: the single-cell alkaline gel electrophoresis (comet) assay, the micronucleus test, and the enumeration of g-H2AX nuclear foci. DNA repair capacity of peripheral blood lymphocytes from 25 cancer-free female heterozygous BRCA1 mutation carriers and 25 noncarrier controls was assessed at baseline and following cell exposure to g -irradiation (2 Gy). We found no significant differences in the mean tail moment, in the number of micronuclei or in the number of g-H2AX nuclear foci between the carriers and non-carriers at baseline, and following g-irradiation. These data suggest that these assays are not likely to be useful in the identification of women at a high risk for breast cancer. British Journal of Cancer (2007) The inheritance of a deleterious mutation in the breast cancer susceptibility gene, BRCA1, has been associated with a lifetime risk of breast cancer of between 45 and 87% (Ford et al, 1998;Antoniou et al, 2003). Genetic, reproductive, and environmental factors have all been suggested to influence breast cancer risk in BRCA1 mutation carriers (reviewed in Narod and Offit (2005)). The use of breast cancer as an endpoint to evaluate the protective role of potential modifying factors is not always feasible. Thus, there is a need to ascertain biomarkers of cancer susceptibility in these women. In turn, the identification of a valid biomarker of breast cancer risk would allow us to identify mutation carriers and help improve our ability to target, and to evaluate the effect of both dietary and lifestyle alterations, as well as, medical diagnostic and therapeutic interventions on breast cancer risk.The BRCA1 protein plays a vital role in maintaining genomic stability because of its key role in the repair of double-stranded DNA breaks by homologous recombination (reviewed in Welcsh et al (2000)). If double-stranded DNA breaks are left unrepaired, or are repaired inaccurately, aberrant chromosome breaks, deletions, and translocations may accumulate. Thus, an impaired cellular response to DNA damage appears to be a plausible mechanism whereby BRCA1 mutation carriers are at an increased risk of breast cancer (Scott, 2004). Hence, the evaluation of an individual's capacity to repair DNA may serve as a biomarker of breast cancer risk in carriers of these mutations.Two previous studies have shown higher levels of chromosomal aberrations and chromosomal breaks among women with a BRCA...

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“…Third, the frequently repeated but questionably supported conclusions about the involvement of specific chromosomes in benzeneassociated leukemias warrant analysis with consideration of the actual published data. Finally, several recent European and Chinese studies have reported a correlation between classic CA and increased cancer risk (Bonassi et al, 1995;Hagmar et al, 1998;Hagmar et al, 1994;Liou et al, 1999).…”

Section: Historical Backgroundmentioning

confidence: 99%