The incidence of unstable chromosome aberrations in peripheral blood lymphocytes from unirradiated and occupationally exposed people

Peripheral blood lymphocytes from unirradiated control subjects and workers exposed within permitted limits to γ-radiation, have been examined for the incidence of dicentric and acentric chromosome aberrations. The results are compared with a review of data published elsewhere. Background levels show inter-laboratory variation and possible reasons for this are discussed. By combining the present data with those from the literature the spontaneous incidence of dicentric aberrations is approx. 0.55 × 10^?3 and for acentrics is 3.7 × 10^?3. In occupationally exposed subjects a significantly higher incidence of aberrations was found. When allowance was made for the turnover of lymphocytes for the period over which each man had worked with radiation a linear dose-effect relationship was apparent. The incidence of dicentrics was 2.22 ± 0.94 × 10^?4 rad^?1 and for all unstable aberrations 8.24 ± 2.8 × 10^?4 rad^?1. These are in reasonable agreement with dose-response data obtained in vitro.     

Polμ deficiency induces moderate shortening of P53−/− mouse lifespan and modifies tumor spectrum

Non-homologous end joining (NHEJ) is the main mechanism for double strand break (DSB) DNA repair. The error-prone DNA polymerase mu (Polμ) is involved in immunoglobulin variable region rearrangement and in general, NHEJ in non-lymphoid cells. Deletion of NHEJ factors in P53^−/− mice, which are highly prone to development of T cell lymphoma, generally increases cancer incidence and shifts the tumor spectrum towards aggressive pro-B lymphoma. In contrast, Polμ deletion increased sarcoma incidence, proportionally reducing pro-B lymphoma development on the P53-deficient background. Array comparative genomic hybridization (aCGH) analyses showed DNA copy number alterations in both P53^−/− and Polμ^−/−P53^−/− lymphomas. Our results also indicate that the increase in sarcoma incidence in Polμ^−/−P53^−/− mice could be associated with Cdk4 and Kub3 amplification and overexpression. These results identify a role for Polμ in the prevention of sarcomagenesis on a murine P53-deficient background, in contrast to most other NHEJ factors.     

Dietary restriction attenuates the accelerated aging phenotype of Sod1−/− mice

Dietary restriction is a powerful aging intervention that extends the life span of diverse biological species ranging from yeast to invertebrates to mammals, and it has been argued that the antiaging action of dietary restriction occurs through reduced oxidative stress/damage. Using Sod1^−/− mice, which have previously been shown to have increased levels of oxidative stress associated with a shorter life span and a high incidence of neoplasia, we were able to test directly the ability of dietary restriction to reverse an aging phenotype due to increased oxidative stress/damage. We found that dietary restriction increased the life span of Sod1^−/− mice 30%, returning it to that of wild-type, control mice fed ad libitum. Oxidative damage in Sod1^−/− mice was markedly reduced by dietary restriction, as indicated by a reduction in liver and brain F₂-isoprostanes, a marker of lipid peroxidation. Analysis of end of life pathology showed that dietary restriction significantly reduced the overall incidence of pathological lesions in the Sod1^−/− mice fed the dietary-restricted diet compared to Sod1^−/− mice fed ad libitum, including the incidence of lymphoma (27 vs 5%) and overall liver pathology. In addition to reduced incidence of overall and liver-specific pathology, the burden and severity of both neoplastic and nonneoplastic lesions was also significantly reduced in the Sod1^−/− mice fed the dietary-restricted diet. These data demonstrate that dietary restriction can significantly attenuate the accelerated aging phenotype observed in Sod1^−/− mice that arises from increased oxidative stress/damage.     

Beneficial effects of carbon monoxide-releasing molecules on post-ischemic myocardial recovery

There is increasing evidence corroborating a protective role of carbon monoxide releasing molecules (CORMs) in injured tissues. Carbon monoxide (CO) carriers have been recently developed as a pharmacological tool to simulate the effect of heme oxygenase-1-derived CO. The effects of CORM-3, a water-soluble CO releaser, on the incidence of reperfusion-induced ventricular fibrillation (VF) and tachycardia (VT) were studied in isolated rat hearts. Hearts were treated with different doses of CORM-3 before the induction of 30 min global ischemia followed by 120 min reperfusion. We found that at concentrations of 25 μM and 50 μM of CORM-3 promoted a significant reduction in the incidence of VF and VT. Thus, the incidence of VF was reduced by 67% (p < 0.05) and 92% (p < 0.05) with 25 μM and 50 μM of CORM-3, respectively. The protective effect of CORM-3 on the incidence of VT followed the same pattern. The antiarrhythmic protection was associated with a marked attenuation in infarct size, significant decreases in cellular Na⁺ and Ca²⁺ gains and K⁺ loss. Consequently, the recovery of post-ischemic function was significantly improved. In conclusion, CORM-3 exerts beneficial effects against ischemia/reperfusion-induced injury through its abilities to release CO which mediates a cardioprotective action by regulating tissue Na⁺, K⁺, and Ca²⁺ levels.     

Consumption of Acidic Water Alters the Gut Microbiome and Decreases the Risk of Diabetes in NOD Mice

Infant formula and breastfeeding are environmental factors that influence the incidence of Type 1 Diabetes (T1D) as well as the acidity of newborn diets. To determine if altering the intestinal microbiome is one mechanism through which an acidic liquid plays a role in T1D, we placed non-obese diabetic (NOD)/ShiLtJt mice on neutral (N) or acidified H₂O and monitored the impact on microbial composition and diabetes incidence. NOD-N mice showed an increased development of diabetes, while exhibiting a decrease in Firmicutes and an increase in Bacteroidetes, Actinobacteria, and Proteobacteria from as early as 2 weeks of age. NOD-N mice had a decrease in the levels of Foxp3 expression in CD4⁺Foxp3⁺ cells, as well as decreased CD4⁺IL17⁺ cells, and a lower ratio of IL17/IFNγ CD4+ T-cells. Our data clearly indicates that a change in the acidity of liquids consumed dramatically alters the intestinal microbiome, the presence of protective Th17 and Treg cells, and the incidence of diabetes. This data suggests that early dietary manipulation of intestinal microbiota may be a novel mechanism to delay T1D onset in genetically pre-disposed individuals.     

Importance of timing,spore concentrations,and levels of spore carrier in applications of Nosema locustae (Microsporida: Nosematidae) for control of grasshoppers

In a study of microbial control of grasshoppers, Nosema locustae was applied to 10-acre plots in 2 replications of 24 treatment combinations in which the factors were (1) times of applications: 4 applications spaced over 22 days; (2) concentrations of spores: 1, 30, and 900 spores/in²; and (3) levels of the spore carrier: 1 and 4 lb wheat bran/acre. The concentrations of spores had the most effect in reducing the densities of grasshoppers and the incidence of infection among the survivors at the last sampling (coincided with the initiation of oviposition), the average reduction in density attributed to application of 1 spore/in² was 21%, that attributed to 30 spores/in² was 46%, and that attributed to 900 spores/in² was 73%. The first and second applications caused the greatest reductions in density; the second, third, and fourth applications produced the highest incidence of infections. Also, a higher incidence of infection was observed among grasshoppers from plots treated with 30 spores/in² on 1 lb bran/acre than from plots treated with 30 spores/in² on 4 lb of bran/acre. Therefore, a ratio of about 0.63–0.94 billion spores/lb bran applied at a rate of 1–1.5 lb/acre (= 100–150 spores/in²) at the time when the principal early summer species are third-instar nymphs would have resulted in overall reductions in density of 50–60%, with 35–50% of the survivors sufficiently infected so that fecundity would probably be affected. The reductions and incidence of infections would be higher in species that readily accept and use wheat bran, among which are some of the more economically important species of grasshoppers.     

Cancer incidence in northern Sweden before and after the Chernobyl nuclear power plant accident

Sweden received about 5 % of the total release of ¹³⁷Cs from the Chernobyl nuclear power plant accident in 1986. The distribution of the fallout mainly affected northern Sweden, where some parts of the population could have received an estimated annual effective dose of 1–2 mSv per year. It is disputed whether an increased incidence of cancer can be detected in epidemiological studies after the Chernobyl nuclear power plant accident outside the former Union of Soviet Socialist Republics. In the present paper, a possible exposure–response pattern between deposition of ¹³⁷Cs and cancer incidence after the Chernobyl nuclear power plant accident was investigated in the nine northernmost counties of Sweden (2.2 million inhabitants in 1986). The activity of ¹³⁷Cs from the fallout maps at 1986 was used as a proxy for the received dose of ionizing radiation. Diagnoses of cancer (ICD-7 code 140-209) from 1980 to 2009 were received from the Swedish Cancer Registry (273,222 cases). Age-adjusted incidence rate ratios, stratified by gender, were calculated with Poisson regression in two closed cohorts of the population in the nine counties 1980 and 1986, respectively. The follow-up periods were 1980–1985 and 1986–2009, respectively. The average surface-weighted deposition of ¹³⁷Cs at three geographical levels; county (n = 9), municipality (n = 95) and parish level (n = 612) was applied for the two cohorts to study the pre- and the post-Chernobyl periods separately. To analyze time trends, the age-standardized total cancer incidence was calculated for the general Swedish population and the population in the nine counties. Joinpoint regression was used to compare the average annual percent change in the general population and the study population within each gender. No obvious exposure–response pattern was seen in the age-adjusted total cancer incidence rate ratios. A spurious association between fallout and cancer incidence was present, where areas with the lowest incidence of cancer before the accident coincidentally had the lowest fallout of ¹³⁷Cs. Increasing the geographical resolution of exposure from nine county averages to 612 parish averages resulted in a two to three times higher value of variance in the regression model. There was a secular trend with an increase in age-standardized incidence of cancer in both genders from 1980 to 2009, but significant only in females. This trend was stronger and statistically significant for both genders in the general Swedish population compared to the nine counties. In conclusion, using both high quality cancer registry data and high resolution exposure maps of ¹³⁷Cs deposition, it was not possible to distinguish an effect of ¹³⁷Cs on cancer incidence after the Chernobyl nuclear power plant accident in Sweden.     

Senegalese sole bone tissue originated from chondral ossification is more sensitive than dermal bone to high vitamin A content in enriched Artemia

Several studies have evaluated the effects of dietary vitamin A (VA) on the incidence of skeletal deformities during early ontogeny of fish, but little is known about its effects on bones depending on their process of ossification (dermal or chondral). We examined the incidence of skeletal deformities along development (30 and 48 dph) by double staining technique, in dermal (haemal and caudal vertebral bodies) and chondral (neural and haemal spines, epural, parahypural and hypurals) bones in Senegal sole post metamorphosed larvae fed with different dietary VA levels (37 000, 44 666, 82 666 and 203 000 UI total VA kg^?1 DW) during Artemia feeding phase (6–37 dph, at 18°C). Results obtained in this study showed that dietary VA disrupted the skeletogenesis in Senegalese sole post metamorphosed larvae by increasing the incidence of skeletal deformities in the axial skeleton and caudal fin complex, which were dependent on both bone morphogenesis and ossification processes. Fish fed with the highest dietary VA content showed the highest incidence of skeletal deformities and its value increased along ontogeny. However, when we compared the incidence of deformities in skeletal structures considering their ossification process, most skeletal structures derived from chondral ossification showed a significant higher increase in deformity incidences in fish fed an excess of VA (44 666, 82 666 and 203 000 UI kg^?1 DW), however within chondral bones, hypurals deformity incidence only increased in sole larvae fed Artemia highest VA content. In contrast, this dietary dose‐response effect was only noted in dermal bones from fish fed the highest dose of VA (203 000 UI kg^?1 DW). In addition, the incidence of deformities in chondral bones increased even when the dietary imbalance of VA was corrected, whereas dermal bones were not affected at later ages. These results indicated that depending on the ossification process from which different skeletal structures are derived, bones might be differentially affected by high dietary VA content. Those directly originated from the connective tissue with a preliminary cartilage stage were more sensitive to dietary VA excess than those formed by intramembranous ossification.     

Association between Birth Order and Emergency Room Visits and Acute Hospital Admissions following Pediatric Vaccination: A Self-Controlled Study

Objective

We investigated the association between a child''s birth order and emergency room (ER) visits and hospital admissions following 2-,4-,6- and 12-month pediatric vaccinations.

Methods

We included all children born in Ontario between April 1^st, 2006 and March 31^st, 2009 who received a qualifying vaccination. We identified vaccinations, ER visits and admissions using health administrative data housed at the Institute for Clinical Evaluative Sciences. We used the self-controlled case series design to compare the relative incidence (RI) of events among 1^st-born and later-born children using relative incidence ratios (RIR).

Results

For the 2-month vaccination, the RIR for 1^st-borns versus later-born children was 1.37 (95% CI: 1.19–1.57), which translates to 112 additional events/100,000 vaccinated. For the 4-month vaccination, the RIR for 1^st-borns vs. later-borns was 1.70 (95% CI: 1.45–1.99), representing 157 additional events/100,000 vaccinated. At 6 months, the RIR for 1^st vs. later-borns was 1.27 (95% CI: 1.09–1.48), or 77 excess events/100,000 vaccinated. At the 12-month vaccination, the RIR was 1.11 (95% CI: 1.02–1.21), or 249 excess events/100,000 vaccinated.

Conclusions

Birth order is associated with increased incidence of ER visits and hospitalizations following vaccination in infancy. 1^st-born children had significantly higher relative incidence of events compared to later-born children.     

Increased incidence of differentiated thyroid carcinoma and detection of subclinical disease

Background

Recent reports from North America and Europe have documented an annual increase in the incidence of differentiated thyroid carcinoma. We sought to investigate the relation between rates of detection, tumour size, age and sex.

Methods

Using the Ontario Cancer Registry, we identified 7422 cases of differentiated thyroid carcinoma diagnosed from Jan. 1, 1990, to Dec. 31, 2001. We obtained pathology reports for a random 10% of the 7422 patients for each year of the study period. The sample represented all Cancer Care Ontario regions. We compared the size of the patients'' tumours by year, sex and age.

Results

As expected, the incidence of differentiated thyroid carcinoma increased over the 12-year period. A significantly higher number of small (≤ 2 cm), nonpalpable tumours were resected in 2001 than in 1990 (p = 0.001). The incidence of tumours 2–4 cm in diameter remained stable. When we examined differences in tumour detection rates by age and sex, we observed a disproportionate increase in the number of small tumours detected among women and among patients older than 45 years.

Interpretation

Our findings suggest that more frequent use of medical imaging has led to an increased detection rate of small, subclinical tumours, which in turn accounts for the higher incidence of differentiated thyroid carcinoma. This suggests that we need to re-evaluate our understanding of the trends in thyroid cancer incidence.Cancer of the thyroid is the most common malignant disease of the endocrine system, and it is the seventh most common cancer affecting women.¹ It is also one of the few cancers with a documented rising incidence, as reported in studies from Canada,² the United States^3–5 and Europe.^6–10 Differentiated thyroid carcinoma is the most common form of thyroid cancer, accounting for about 90% of all cases, and includes both papillary thyroid carcinomas and follicular carcinomas.¹There has been much speculation about why the incidence of differentiated thyroid carcinoma is rising. Some researchers have suggested that potential risk factors include radiation exposure,^11–13 iodine deficiency,^8,9 family history of thyroid cancer, and personal history of goiter or thyroid nodule.³ It has also been proposed that at least some of the increase may be related to head and neck radiation therapy used to treat benign childhood conditions between 1910 and 1960.¹⁴ Studies examining the long-term incidence of thyroid cancer after radiation exposure have suggested that the risk may be as high as 15%.^13,15,16 About 74% of newly diagnosed cases of differentiated thyroid carcinoma involve women¹ and it has been suggested that certain female hormonal and reproductive factors may play a role.^17,18An alternative explanation is that the rise in incidence may be due to increased detection of subclinical diseases from greater use of medical imaging. A recent retrospective cohort study in the United States examined the change in size of resected thyroid tumours from 1973 to 2002.⁴ Using data from the National Cancer Institutes'' Surveillance Epidemiology and End Results (SEER) Cancer Statistic database, investigators found a significant decrease in tumour size over time and concluded that the apparent increase in disease incidence was due to increased detection of small tumours rather than an actual increase in the number of thyroid cancers.We sought to assess the incidence of thyroid cancer over a 12-year period in Ontario. We hypothesized that if the rising incidence was due to increased detection of subclinical tumours, small tumours would account for an increasing proportion of tumours detected. On the other hand, if environmental factors caused the increased incidence, the distribution of tumour size would remain stable over time. We tested our hypothesis by comparing differences in detection rates by sex and age within the study population.     

Incidence of Menkes disease

Summary We have calculated the incidence of Menkes disease for Denmark, France, The Netherlands, the United Kingdom and West Germany, based on known Menkes patients born during the time period 1976–87. Considering live-born Menkes patients, the combined incidence for these five countries is 1 Menkes patient per 298000 live-born babies. If the number of affected aborted fetuses are taken into account, the incidence is 1 Menkes per 254000 live-born babies. This incidence, which is 2–4 times lower than earlier published incidence figures, places Menkes disease as an extremely rare disease. The mutation rate for Menkes disease is estimated to be 1.96 × 10^–6, based on the number of isolated Menkes cases born during the time period 1976–87 and the total number of newborn males during this time.     

Synergy between tetrandrine and FK 506 in prevention of diabetes in BB rats

Delayed administration of tetrandrine, a novel broad-spectrum anti-inflammatory agent, to BB rats at a dosage schedule of 20 mg kg ⁻¹ day ⁻¹ from 79 days of age reduced the cumulative incidence of diabetes from 73.1 to 41.7% (p<0.01). Brief treatment with the potent immunosuppressive agent FK506 at a dosage schedule of 0.5 mg kg⁻¹ day ⁻¹ from 79 days of age for 5 days had no significant effect on the cumulative incidence of diabetes (66.7%, p > 0.1). However, the combination of tetrandrine and FK506 in the afore-mentioned dosage schedules reduced the incidence of diabetes to only 3.6% (p <0.001). These results suggest that the strong synergy between tetrandrine and FK506 may offer a safe and effective therapeutic strategy for the treatment of patients with recent onset or imminent IDDM.     

Incidence and mortality rates of keratinocyte carcinoma from 1998–2017: a population-based study of sex differences in Ontario,Canada

Background:Keratinocyte carcinoma is the most common malignant disease, but it is not captured in major registries. We aimed to describe differences by sex in the incidence and mortality rates of keratinocyte carcinoma in Ontario, Canada.Methods:We conducted a population-based retrospective study of adults residing in Ontario between Jan. 1, 1998, and Dec. 31, 2017, using linked health administrative databases. We identified the first diagnosis of keratinocyte carcinoma using a validated algorithm of health insurance claims, and deaths related to keratinocyte carcinoma from death certificates. We calculated the incidence and mortality rates of keratinocyte carcinoma, stratified by sex, age and income quintile. We evaluated trends using the average annual percentage change (AAPC) based on joinpoint regression.Results:After decreasing from 1998 to 2003, the incidence rate of keratinocyte carcinoma increased by 30% to 369 per 100 000 males and 345 per 100 000 females in 2017 (AAPC 1.9%, 95% confidence interval [CI] 1.7 to 2.1 from 2003 to 2017). The incidence rate was higher in females younger than 55 years, but higher in males aged 55 years or older. Between 2008 and 2017, the incidence rate rose faster in females than males aged 45–54 years (AAPC 1.2% v. 0.5%, p = 0.01) and 55–64 years (1.2% v. 0.1%, p < 0.01). The incidence was higher in males than females in the higher income quintiles. Between 1998 and 2017, the mortality rate of keratinocyte carcinoma was 1.8 times higher in males than females, on average, and rose 4.8-fold overall (AAPC 8.9%, 95% CI 6.4 to 11.4 in males; 8.0%, 95% CI 5.3–10.8 in females).Interpretation:The population burden of keratinocyte carcinoma is growing, and the incidence and mortality rates rose disproportionately among certain sex- and age-specific groups. This warrants further investigation into causal factors and renewed preventive public health measures.

Keratinocyte carcinoma comprises basal and squamous cell carcinomas, and is the most common malignant disease in Canada and the United States.^1–5 Although keratinocyte carcinoma has a low mortality rate, it is associated with substantial morbidity and impaired quality of life.^2,6,7 Among cancers, it also ranks fifth in health care costs in the US.⁸Epidemiological studies of keratinocyte carcinoma in North America are limited by its exclusion from most cancer registries. ⁹ Previous studies found that higher overall incidence of keratinocyte carcinoma is associated with male sex,^10–14 older age^15–17 and higher socioeconomic status.^18–21 However, differences in the incidence and mortality rates of keratinocyte carcinoma by sex in relation to age and socioeconomic status have not been well characterized.A better understanding of the epidemiology of keratinocyte carcinoma in Canada and differences by sex would inform public health initiatives, health services policy and patient education strategies. This is particularly relevant now, given the recent regulatory approval of systemic immunotherapies for locally advanced or metastatic squamous and basal cell carcinoma.^22–25 Our objective was to identify the population-based incidence and mortality trends of keratinocyte carcinoma in Ontario, Canada over 2 decades and to evaluate sex differences.     

Immunogenetic and ontogenetic studies of chickens with selective IgA deficiency and autoimmune thyroiditis

In addition to spontaneous hypothyroidism and autoimmune thyroiditis, chickens of the obese strain (OS) have a high incidence of selective IgA deficiency. Elevated levels of serum IgM also occur in many OS chickens. The IgA deficiency begins by 2 weeks, the age when hypothyroidism is developing. Like thyroiditis, a greater incidence of IgA deficiency was noted in OS birds homozygous for the B¹ allele than for the B⁴ allele of the major histocompatibility locus. Although IgA deficiency occurs in both sexes, it is found in a higher frequency in females than males (2:1). An abnormal ontogenesis of immunological competence may influence both traits.     

Duchenne muscular dystrophy

Summary By a general survey in the hospitals of northeast Italy, Duchenne cases have been located and identified over a 20-year period.In a more restricted area screening for Duchenne carriers has been carried out in affected families. This procedure made possible an exact estimate of the incidence rate, prevalence rate, and mutation rate in a large sample of population. Prevalence rate was found to be 34x10^-6, incidence rate about 28x10^-5, while mutation rate was found lower than 50x10^-6 by the direct method.The discrepancy between the results obtained by the Haldane formula and those obtained by the direct method for the estimate of the mutation rate is discussed.     

Tumour Induction by Cell-free Extracts derived from Mice with Graft versus Host Disease

A SUBSTANTIAL proportion of inbred mice, in which a protracted form of the graft versus host reaction (GVHR) is induced, eventually develop lymphoreticular tumours¹. This experimental mouse model can be used to study the role of immune reactions in cancer induction. One possibility is that the immune disturbance activates a latent oncogenic virus. That such activation can occur has been demonstrated in C57BL mice². In this strain, with its low spontaneous leukaemic incidence, thymic lymphomas are induced by an irradiation-activated leukaemogenic virus. In man, there is suggestive evidence that Burkitt's lymphoma may be caused by a combination of virus infection and immunological stimulation³.     

The foliar chemical profile of criollo avocado, Persea americana var. drymifolia (Lauraceae), and its relationship with the incidence of a gall-forming insect, Trioza anceps (Triozidae)

The role of phytochemical diversity in plant defense was studied using the specialist herbivore Trioza anceps Tuthill (avocado gall-forming insect), and the volatile fraction of the foliar chemicals of its host, the creole avocado (Persea americana var. drymifolia (Schect. &; Cham.) Blake). Two hypotheses were tested: a) plant defense is determined by phytochemical diversity, and b) plant defense is determined by single compounds or specific blends of compounds. Simple and multiple regressions and a size and shape analysis (which considers the compounds relative and absolute concentrations within the leaf blend) were used to test these hypotheses. Simple regressions of gall incidence and chemical diversity and the tree origin elevation and latitude were very weak. The linear multiple regression to explain gall incidence with 33 foliar compounds and geographical data produced a model with low predictive power (R² = 0.13). The size and shape analysis showed intraspecific variation in leaf chemical profiles among five tree groups, classified by the number of galls per 10 cm² of leaf. Discriminant analysis separated clearly the tree groups’ chemical profiles through specific compounds. These results suggest that the gall incidence is associated with specific chemical profiles, rather than to high or low foliar phytochemical diversity.     

Optimal Electrical Stimulus for Prevention of Deep Vein Thrombosis

The most effective electrical stimulus to the calf muscles which prevents stasis in the soleal veins during operation was determined. This was subsequently used in a clinical trial and was shown to produce a 92% relative reduction in the incidence of deep vein thrombosis as determined by the ¹²⁵I-fibrinogen test.     

Expansion of CD11b+Ly6G+Ly6Cint cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains NK cell effector functions

The progesterone analog medroxyprogesterone acetate (MPA) is widely used as a hormone replacement therapy in postmenopausal women and as contraceptive. However, prolonged administration of MPA is associated with increased incidence of breast cancer through ill-defined mechanisms. Here, we explored whether exposure to MPA during mammary tumor growth affects myeloid-derived suppressor cells (MDSCs; CD11b⁺Gr-1⁺, mostly CD11b⁺Ly6G⁺Ly6C^int and CD11b⁺Ly6G^?Ly6C^high cells) and natural killer (NK) cells, potentially restraining tumor immunosurveillance. We used the highly metastatic 4T1 breast tumor (which does not express the classical progesterone receptor and expands MDSCs) to challenge BALB/c mice in the absence or in the presence of MPA. We observed that MPA promoted the accumulation of NK cells in spleens of tumor-bearing mice, but with reduced degranulation ability and in vivo cytotoxic activity. Simultaneously, MPA induced a preferential expansion of CD11b⁺Ly6G⁺Ly6C^int cells in spleen and bone marrow of 4T1 tumor-bearing mice. In vitro, MPA promoted nuclear mobilization of the glucocorticoid receptor (GR) in 4T1 cells and endowed these cells with the ability to promote a preferential differentiation of bone marrow cells into CD11b⁺Ly6G⁺Ly6C^int cells that displayed suppressive activity on NK cell degranulation. Sorted CD11b⁺Gr-1⁺ cells from MPA-treated tumor-bearing mice exhibited higher suppressive activity on NK cell degranulation than CD11b⁺Gr-1⁺ cells from vehicle-treated tumor-bearing mice. Thus, MPA, acting through the GR, endows tumor cells with an enhanced capacity to expand CD11b⁺Ly6G⁺Ly6C^int cells that subsequently display a stronger suppression of NK cell-mediated anti-tumor immunity. Our results describe an alternative mechanism by which MPA may affect immunosurveillance and have potential implication in breast cancer incidence.