Acute restraint stress increases the frequency of vinblastine-induced micronuclei in mouse bone marrow cells

Abstract

Acute physiological stress induces remarkable effects on the nervous, endocrine, and immune systems and also on cellular metabolism and cell division processes. Stress-induced instability of cellular mechanisms might play an important role in increasing cell division disorders. In this study, a relationship between stress and micronucleus (MN) induction in mouse (balb/c) bone marrow cells following vinblastine treatment, or stress or stress and vinblastine treatment in comparison to a non-stressed control group was investigated. In order to test the effects of treatments on MN induction, an in vivo MN assay was performed on bone marrow cells. The results revealed a significantly greater increase in MNs in bone marrow cells (polychromatic erythrocytes) from the stressed/vinblastine treated mice. The data indicate the ability of exposure to an emotional stressor to enhance the damaging actions on bone marrow cells of an aneugenic agent.

Hydrocortisone Increases the Vinblastine-Induced Chromosomal Damages in L929 Cells Investigated by the Micronucleus Assay on Cytokinesis-Blocked Binucleated Cells

“…A synergistic effect of acute restraint stress was reported on VIN-induced Mn frequency in an in vivo study [20]. However, we could not conclude if the increase in the Mn frequency was because of stress-induced malfunctioning of the cellular mechanisms monitoring the genetic integrity or perhaps by increased blood pressure causing more VIN to enter the bone marrow.…”

“…Genotoxic effects of stress have already been suggested in an in vivo study [20]. Prolonged stressed mice, treated with doses of vinblastine exhibited a higher frequency of Mn in their polychromatic erythrocytes compared to nonstressed ones.…”

Cortisol Is Not Associated with Telomere Shortening or Chromosomal Instability in Human Lymphocytes Cultured under Low and High Folate Conditions

“…Previous findings have shown that, under certain conditions, abnormally elongated telomeres can be as dysfunctional as critically short telomeres, leading to increased CIN and disease risk [ 17 , 46 – 48 ]. In vitro and animal studies have also suggested that stress hormones may induce damage to DNA [ 29 , 49 – 51 ]. Short term (< 30 minutes) exposure to cortisol in vitro was shown to disrupt DNA repair in murine 3T3 cells exposed to UV, including transcriptional modulation of 21 genes involved, directly or indirectly, in DNA repair [ 49 ].…”

“…In FA replete cultures cortisol had no effect on the frequency of MN or NBuds, but a trend for a reduction in FUS and NPB was observed. Previous in vivo findings by Malvandi et al showed that restraint stress in mice increased the induction of MN in bone marrow of vinblastine-treated animals, compared with controls [ 29 ]. Evidence by York et al also suggested a link between stress exposure and DNA damage, showing an increased frequency of MN in adults who had suffered social abuse in childhood [ 10 ].…”

“…Direct intramuscular injection of cortisol, or its precursor ACTH, resulted in a 23% and 24% reduction in serum folate, respectively [ 28 ]. Both psychological stress and folate deficiency have been associated in vivo with increased DNA damage in the form of micronuclei (indicative of chromosome breakage due to DNA double strand breaks or chromosome malsegregation) [ 10 , 15 , 29 ]. Furthermore, we have shown that chronic long term folate deficiency in vitro leads to both dysfunctional long telomeres, and loss of telomeres due to accumulation of terminal deletions [ 17 ].…”