'Spontaneous' genetic damage in man: evaluation of interindividual variability, relationship among markers of damage, and influence of nutritional status

MacGregor, James T.; Wehr, Carol M.; Hiatt, Robert A.; Peters, Beverly; Tucker, James D.; Langlois, Richard G.; Jacob, Robert A.; Jensen, Ronald H.; Yager, Janice W.; Shigenaga, Mark K.; Frei, Balz; Eynon, Barrett P.; Ames, Bruce N.

doi:10.1016/s0027-5107(97)00070-5

Cited by 98 publications

(54 citation statements)

References 14 publications

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“…Similar to other reports (3,19,41), we observed a considerable range of MN CD71+ frequencies in presumably healthy volunteers (0.04% -0.28%). Linear regression analyses demonstrated that the variation in these baseline readings could not be correlated with age, or levels of B 12 and folate.…”

Section: Healthy Subjectssupporting

confidence: 92%

“…Linear regression analyses demonstrated that the variation in these baseline readings could not be correlated with age, or levels of B 12 and folate. This is in contrast to other studies reporting significant effects for each of these factors on the incidence of micronuclei (3,(31)(32). These discrepancies may be related to differences in target cells (erythroblasts versus lymphocytes) or some other factor(s), such as the relative homogeneity of these subjects, the great majority of which exhibited normal/ healthy B 12 and folate levels (all recruited from a University hospital setting).…”

Section: Healthy Subjectscontrasting

confidence: 89%

“…The average frequency of MN CD71+ in the plasma of healthy subjects was similar (although somewhat lower) to previously reported values observed in the bone marrow or in the peripheral blood circulation of splenectomized human subjects (0.12% compared with approximately 0.2% to 0.3%, respectively) (3,(38)(39)(40)(41)(42)(43). This is likely related to splenic filtration function, which may not be fully negated by restricting analyses to Retic CD71+ (44).…”

Section: Healthy Subjectssupporting

confidence: 87%

“…In vivo cytogenetic damage assays have proven useful for myriad human health applications, including assessments of product safety, occupational and environmental exposures, dietary and life-style choices, and the effect of genetic polymorphisms on chromosomal integrity (1)(2)(3)(4)(5)(6). Furthermore, the current gold standard techniques for estimating radiation dose in the absence of physical dosimetry are based on chromosomal damage endpoints, especially dicentric and micronucleus formation in peripheral blood lymphocytes (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

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Automated human blood micronucleated reticulocyte measurements for rapid assessment of chromosomal damage

Dertinger¹,

Miller²,

Brewer³

et al. 2007

Mutation Research/Genetic Toxicology and Environmental Mutagene

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This study evaluated the utility of human blood micronucleated reticulocyte (MN CD71+ ) frequency measurement as a cytogenetic damage biomarker. The analytical methodology was flow cytometry in conjunction with a previously described three color fluorescence labeling technique that includes anti-CD71 to focus analyses on the most immature fraction of reticulocytes [Dertinger et al., Environ. Molec. Mutagen., 44:427-435 (2004)]. Blood specimens from fifty self-reported healthy adult volunteers were studied. In addition to MN CD71+ measurements, blood plasma folate and B 12 levels were assessed, since these variables tend to influence other indices of cytogenetic damage. Timecourse data are also provided for ten cancer patients undergoing treatment. For these subjects, frequency of MN CD71+ was measured immediately before therapy, and daily during the first week of chemotherapy and/or fractionated radiotherapy. For the group of healthy volunteers, the variables of age, and folate and B 12 levels demonstrated no significant effect on MN CD71+ frequency. In addition, no difference was observed between pre-treatment MN CD71+ values for cancer patients compared with healthy volunteers. Regarding chemotherapy and/or partial body radiotherapy, elevated frequencies were observed upon initiation of treatment for 9 of the 10 patients studied. Maximal effects were observed three to five days following initiation of therapy. The largest increases in frequency of MN CD71+ (up to 25.9-fold) were observed in those patients exposed to anti-neoplastic drugs, presumably due to the systemic red marrow exposure provided by these agents. Taken together, these data support the hypothesis that the MN CD71+ endpoint represents a valuable biomarker of cytogenetic damage that does not require cell culture or microscopy-based scoring.

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Section: Healthy Subjectssupporting

confidence: 92%

Section: Healthy Subjectscontrasting

confidence: 89%

Section: Healthy Subjectssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Automated human blood micronucleated reticulocyte measurements for rapid assessment of chromosomal damage

Dertinger¹,

Miller²,

Brewer³

et al. 2007

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…The advent of this new technology was important for our study design because, although the mouse peripheral blood erythrocyte micronucleus test has been used routinely for decades to evaluate genotoxicity (Heddle et al, 1991;OECD, 1997;MacGregor et al, 1990;Albertini et al, 2000;Witt et al, 2000;Hayashi et al, 1994), there has not been a corresponding human assay because the human spleen, unlike the mouse spleen, rapidly removes damaged erythrocytes from circulation. Thus, until recently, experimental evidence of genotoxicity obtained through use of routine rodent erythrocyte MN studies could not be confirmed in the same cell type in humans unless the human subject had undergone splenectomy (MacGregor et al, 1997). However, this new flow cytometry-based test method enables the identification, selection, and evaluation of the youngest fraction of reticulocytes (<48 hr old), representing approximately10% of all circulating reticulocytes, before the effects of splenic selection have much impact on the frequency of MN-RET.…”

Section: Introductionmentioning

confidence: 99%

Elevated frequencies of micronucleated erythrocytes in infants exposed to zidovudine in utero and postpartum to prevent mother‐to‐child transmission of HIV

Witt

Cunningham

Patterson

et al. 2007

Environ and Mol Mutagen

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Zidovudine-based antiretroviral therapies (ART) for treatment of HIV-infected pregnant women have markedly reduced mother-to-child transmission of the human immunodeficiency virus (HIV-1) from ~25% to <1%. However, zidovudine (ZDV; AZT), a nucleoside analogue, induces chromosomal damage, gene mutations, and cancer in animals following direct or transplacental exposures. To determine if chromosomal damage is induced by ZDV in infants exposed transplacentally, we evaluated micronucleated reticulocyte frequencies (%MN-RET) in 16 HIVinfected ART-treated mother-infant pairs. Thirteen women received prenatal ART containing ZDV; 3 received ART without ZDV. All infants received ZDV for 6 weeks postpartum. Venous blood was obtained from women at delivery, and from infants at 1-3 days, 4-6 weeks, and 4-6 months of life; cord blood was collected immediately after delivery. Ten cord blood samples (controls) were obtained from infants of HIV-uninfected women who did not receive ART. %MN-RET was measured using a single laser 3-color flow cytometric system. Ten-fold increases in %MN-RET were seen in women and infants who received ZDV-containing ART prenatally; no increases were detected in 3 women and infants who received prenatal ART without ZDV. Specifically, mean %MN-RET in cord blood of ZDV-exposed infants was 1.67±0.34 compared with 0.16±0.06 in non-ZDV ARTexposed infants (P=0.006) and 0.12±0.02 in control cord bloods (p<0.0001). %MN-RET in ZDVexposed newborns decreased over the first 6 months of life to levels comparable to cord blood controls. These results demonstrate that transplacental ZDV exposure is genotoxic in humans. Longterm monitoring of HIV-uninfected ZDV-exposed infants is recommended to ensure their continued health.

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Human cytogenetic biomonitoring using flow-cytometric analysis of micronuclei in transferrin-positive immature peripheral blood reticulocytes

Abramsson‐Zetterberg

Zetterberg

Bergqvist

et al. 2000

Environ. Mol. Mutagen.

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'Spontaneous' genetic damage in man: evaluation of interindividual variability, relationship among markers of damage, and influence of nutritional status

Cited by 98 publications

References 14 publications

Automated human blood micronucleated reticulocyte measurements for rapid assessment of chromosomal damage

Automated human blood micronucleated reticulocyte measurements for rapid assessment of chromosomal damage

Elevated frequencies of micronucleated erythrocytes in infants exposed to zidovudine in utero and postpartum to prevent mother‐to‐child transmission of HIV

Human cytogenetic biomonitoring using flow-cytometric analysis of micronuclei in transferrin-positive immature peripheral blood reticulocytes

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