Effects of daily activities on ambulatory blood pressure during menstrual cycle in normotensive women

The purpose of this study was to determine whether (1) there is a menstrual phase effect on blood pressure (BP) and heart rate (HR), and (2) the effects of physical effort, posture, or moods on BP and HR is mediated by the menstrual phase. Twelve normotensive women, aged between 28 and 50, with normal menstrual cycles were studied. BP was measured at 30- to 60-min intervals during a 24-hr period using an ambulatory BP monitor on Days 1, 8, 15, and 22 of the menstrual cycle. Participants were asked to report their posture, physical effort, and mood (annoyed, tense, and happy) on 5-point Likert-type scales each time the ambulatory BP monitor took measurements. Systolic BP (SBP) was lower on Day 8 of the cycle. Diastolic BP (DBP) and HR were lower on Days 1 and 8. Daytime SBP was affected by the time of the day and posture, but not by moods, whereas daytime DBP was affected by posture and levels of tenseness. The level of physical effort only affected HR, not BP. The average daytime physical and emotional variables had little influence over the average daytime BP. In 1 normotensive women with a normal menstrual cycle, SBP was lower during the follicular phase and DBP and HR were lower during the follicular phase and menstruation even after controlling the effects of other factors. Physical activity or moods had only momentary effects on BP or HR. A cross-validation statistical method used is suggested to study how individuals are affected by various factors. With the use of this method, the inclusion of menstrual phase in the model improved the prediction of SBP for 5 out of the 12 women studied.     

Timing of surgery during the menstrual cycle and prognosis of breast cancer

There are conflicting reports on the differential effect of surgery performed during the two phases of the menstrual cycle, namely, follicular and luteal, and prognosis of operable breast cancer. A statistical meta-analysis of the published evidence suggests a modest survival benefit of 15+/-4% when the operation is performed during the luteal phase. Further research in this area might provide a novel avenue to understand the natural history of breast cancer. A spin off from these studies might be the understanding of the importance of events that occur at the time of surgery in determining long term prognosis.     

月经周期对女性睡眠-觉醒和静息-活动的影响

目前有关月经周期对睡眠影响的研究结果并不一致,而对月经周期中昼夜睡眠-觉醒及静息-活动节律尚缺乏系统性的研究.本研究旨在观察正常育龄期女性月经周期中睡眠-觉醒及静息-活动昼夜节律的变化.我们采用静息-活动监测仪(actigraphy)和睡眠日志,调查了12个自然生活状态下健康育龄期妇女在月经周期不同阶段,即行经期、围排卵期、黄体早期及黄体晚期中睡眠与活动节律的变化.结果显示,睡眠-觉醒节律参数在四期之间无统计学显著差异;而静息-活动节律方面,所有受试女性静息-活动节律的平均日周期长度为(24.01±0.29)h,并且四期之间无显著性差异.行经期日间稳定系数(interdaily stability,IS)比黄体早期显著增加(P＜0.05).黄体早期日间活动开始时间明显较黄体晚期提前(P＜0.05);黄体早期的活动峰值时相比围排卵期显著提前(P＜0.05).月经周期可以影响静息-活动昼夜节律时相.而总体静息-活动数量与质量未发生显著变化;健康育龄期妇女在月经周期的各阶段中睡眠-觉醒节律亦无明显变异.     

Urinary immunoreactive estrogen and pregnanediol-3-glucuronide during the normal menstrual cycle of the female lowland gorilla (Gorilla gorilla)

Urine samples were taken daily during 22 menstrual cycles of six normal adult female gorillas. Urine was analyzed for total immunoreactive estrogens (E_t) and pregnanediol-3-glucuronide (PdG) and indexed by creatinine (Cr). An average cycle length of 32 ± 1 days (mean ± SE) with a range of 25–42 days is reported. Estrogen values range from 4 to 128 ng/mg Cr and show a midcycle peak and a midluteal rise. PdG values range from 0.01 to 2.4 μg/mg Cr and display a low, flat follicular phase followed by a luteal elevation. The follicular phase is 19.5 ± 1 days in length (range 11–30 days) and accounts for the variation in cycle length. The luteal phase is 12.3 ± 0.3 days long (range 10–14 days). In contrast to previous studies, PdG levels rise two days before the estrogen peak. The results from the present study are compared with information available on the gorilla, chimpanzee, and human. The accuracy of various alignment methods is discussed, as well as the importance of the methods presented in this study for the captive propagation of gorillas.     

Luteinizing hormone receptors in ovaries of the cynomolgus monkey (Macaca fascicularis) during the menstrual cycle

Ovarian luteinizing hormone (LH) receptors were characterized using ovarian tissues from 17 cynomolgus monkeys at different phases of the menstrual cycle. Low binding affinity receptors for ¹²⁵I-LH were observed throughout the menstrual cycle. The binding affinity of these receptors for LH (< 12 × 10¹⁰ M^?1) was approximately the same as that of ovarian LH receptors previously reported in human and nonhuman primates. In addition, high-affinity receptors (17?85 × 10¹⁰ M^?1) were also detected at the mid-luteal phase, during which a large functional corpus luteum was present. Thus the high-affinity LH receptors appear with the formation of the corpus luteum and disappear with its regression. Almost no fluctuation of binding capacity was observed throughout the menstrual cycle (32?112 fmol/ mg of ovarian tissue). The high-affinity LH receptor was judged to be derived from the functional corpus luteum.     

月经周期不同阶段游离皮质醇昼夜节律的变化

为了研究皮质醇分泌的昼夜节律在月经周期中的变化,实验对15位月经周期正常的育龄期健康妇女,在月经周期的不同阶段分别于24h内每隔两小时采样,检测唾液昼夜游离皮质醇水平。采用非线性回归分析模型分析皮质醇昼夜节律。结果显示,皮质醇昼夜节律在整个月经周期都具有复杂的明显受到亚节律(ultradian)影响的分泌形式;与月经期相比,围排卵期和黄体晚期昼夜节律波峰宽度(peak-width)明显减低(P=0．005与0．031),而昼夜节律波谷(trough)有抬高趋势(P=0．0622与0．066);黄体晚期的亚节律波幅(ultradian amplitude)与月经期相比显著减低(P=0．002)而与围排卵期相比有减低趋势(P=0．05)。这些结果提示月经周期的不同阶段对皮质醇分泌的昼夜节律有影响。     

Serum levels of gonadotropins and gonadal steroids,including testosterone,during the menstrual cycle of the chimpanzee (Pan troglodytes)

The objective of this study was to expand the data on menstrual cycle serum hormone patterns in female common chimpanzees, both in terms of the number of cycles analyzed and by the addition of data on testosterone levels. Samples were obtained from 11 unanesthetized animals trained for conscious blood withdrawal. LH, FSH, 17β-estradiol (E₂), progesterone (P), and testosterone (T) were measured by radioimmunoassay, genital swelling was recorded, and menstrual blood was noted. Concurrent midcycle elevations in LH and FSH and luteal phase elevations in progesterone suggested that the cycles were ovulatory. Detumescence of genital swelling occurred about 3 days after the midcycle LH peak, 1 day after the luteal phase nadir in E₂, and 1 day after P levels exceeded 5 ng/ml. These relationships provide further support for the use of genital swelling in monitoring progress of the menstrual cycle. The hormone patterns in the chimpanzees closely resembled those of the human females, but E₂ and T levels were higher. The levels of E₂ and T were higher and the midcycle elevation in T was broader in the chimpanzee than in gorillas and orangutans. This is of interest because E₂ and T are implicated in the regulation of mating, and chimpanzees mate over a greater portion of the cycle than the other apes. These data indicate the need for further study of hormonal contributions to the different patterns of mating in the great apes. They also support the use of the female common chimpanzee as a model for the human female in endocrine studies of the menstrual cycle.     

Diurnal and menstrual cycles in body temperature are regulated differently: A 28-day ambulatory study in healthy women with thermal discomfort of cold extremities and controls

Diurnal cycle variations in body-heat loss and heat production, and their resulting core body temperature (CBT), are relatively well investigated; however, little is known about their variations across the menstrual cycle under ambulatory conditions. The main purpose of this study was to determine whether menstrual cycle variations in distal and proximal skin temperatures exhibit similar patterns to those of diurnal variations, with lower internal heat conductance when CBT is high, i.e. during the luteal phase. Furthermore, we tested these relationships in two groups of women, with and without thermal discomfort of cold extremities (TDCE). In total, 19 healthy eumenorrheic women with regular menstrual cycles (28–32 days), 9 with habitual TDCE (ages 29?±?1.5 year; BMI 20.1?±?0.4) and 10 controls without these symptoms (CON: aged 27?±?0.8 year; BMI 22.7?±?0.6; p?<?0.004 different to TDCE) took part in the study. Twenty-eight days continuous ambulatory skin temperature measurements of distal (mean of hands and feet) and proximal (mean of sternum and infraclavicular regions) skin regions, thighs, and calves were carried out under real-life, ambulatory conditions (i-Buttons® skin probes, sampling rate: 2.5?min). The distal minus proximal skin temperature gradient (DPG) provided a valuable measure for heat redistribution from the core to the shell, and, hence, for internal heat conduction. Additionally, basal body temperature was measured sublingually directly after waking up in bed. Mean diurnal amplitudes in skin temperatures increased from proximal to distal skin regions and the 24-h mean values were inversely related. TDCE compared to CON showed significantly lower hand skin temperatures and DPG during daytime. However, menstrual cycle phase did not modify these diurnal patterns, indicating that menstrual and diurnal cycle variations in skin temperatures reveal additive effects. Most striking was the finding that all measured skin temperatures, together with basal body temperature, revealed a similar menstrual cycle variation (independent of BMI), with highest and lowest values during the luteal and follicular phases, respectively. These findings lead to the conclusion that in contrast to diurnal cycle, variations in CBT variation across the menstrual cycle cannot be explained by changes in internal heat conduction under ambulatory conditions. Although no measurements of metabolic heat production were carried out increased metabolic heat generation during the luteal phase seems to be the most plausible explanation for similar body temperature increases.     

A comparison of the behavior of Macaca fascicularis and Macaca mulatta in relation to the menstrual cycle

Observations on oppositely sexed pairs of M. fascicularis and M. mulatta revealed certain differences. M. fascicularis showed single-mount copulations, higher potency, less grooming activity, and milder but more frequent aggressive exchanges than the rhesus monkey. These differences might be due to the lower dominance gradient between the sexes and less sexual dimorphism in M. fascicularis than in M. mulatta. There were changes in the sexual, grooming, and aggressive interaction in relation to the menstrual cycle, indicating the suitability of M. fascicularis for hormone-behavior studies. Comparison of data from 30 and 60 min tests showed that important behavioral changes did not become apparent unless animals were given enough time to interact.     

Variations in the concentrations of androstenedione in peripheral plasma of women the day and during the menstrual cycle

The target tissues (e.g., hypothalamus, pituitary, uterus and vagina) of mature female ovariectomized rats show selective uptake of radioactivity in one hour after the injection of 6,7, ³H-estradiol-17β in a dose of 0.1 μg per 100 g body weight. Injection of 100 μg norethindrone or norgestrel per 100 g body weight 15 min before or 15 min after the administration of tritiated estradiol reduced the radioactivity in most target tissues, and also in the non-target tissues to a lesser extent. The uptake of radioactivity in the pituitary and uterus is reduced more by norethindrone than by norgestrel treatment when these Steroids were injected 15 min after estradiol-17β injection. It appears that there exists a competitive inhibition of estradiol-17β by these contraceptive Steroids in the rat. It is speculated that such competition with estradiol-17β may be an inherent property of the 17-substituted 19-nortestosterone group of Steroids.     

Patterns of changes in proteins in the peritoneal fluid of women during the periovulatory phase of the menstrual cycle

During a laparoscopy that was performed between Day -6 and Day +9 of the cycle as related to the day of the LH peak (Day 0), the peritoneal fluid of 100 healthy female volunteers of proven fertility was collected and analysed. Peritoneal fluid volume and concentrations of total protein, albumin, alpha 1-, alpha 2-, beta- and gamma-globulins, IgA, IgG, IgM, haptoglobulin, acid-alpha 1-glycoprotein, alpha 1-antitrypsin, alpha 2-macroglobulin, C3-, C4- and C-reactive protein were determined. The peritoneal fluid volume and the concentrations of most proteins analysed showed an increase during the post-ovulatory phase of the period investigated. The peritoneal fluid:serum ratio of each individual protein showed a significant inverse correlation with its molecular weight. This confirms the assumption that peritoneal fluid is mainly an exudation product, most probably of ovarian origin.     

Diurnal rhythms of free estradiol and cortisol during the normal menstrual cycle in women with major depression

To investigate whether depression is accompanied by changes in diurnal rhythms of free estradiol and cortisol in different phases of the menstrual cycle, we measured these two hormone levels in saliva samples collected every 2 h for 24 h from 15 healthy normally cycling women and 12 age-matched normally cycling women suffering from major depression taking antidepressants. The assessments were repeated four times over one menstrual cycle: during menstruation and in the late follicular/peri-ovulating, early to mid-luteal and late luteal phases, respectively. Quantification with a nonlinear periodic regression model revealed distinct diurnal rhythms in free estradiol and free cortisol in all subjects. For the diurnal cortisol rhythm, significant differences were found in the peak-width and ultradian amplitude among different menstrual phases, both in controls and depressed patients, while no significant differences were found between the two groups. The diurnal estradiol rhythm, on the other hand, was quite consistent among different menstrual phases within both groups, while the depressed patients had overall larger amplitudes than controls, which is negatively correlated with disease duration. Significant positive correlations between the two hormone rhythms were found for 24-h mean level (mesor), peak, and trough in late luteal phase, and for ultradian harmonics in early to mid-luteal phase in controls, but only for ultradian harmonics in late follicular/peri-ovulating phase and for acrophase in the menstruation phase in depressed patients. A sub-analysis was also performed in patients who received Fluoxetine (n = 7). The findings implicate a close correlation between the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis, both of which may be involved in depression.     

Incidence of atresia or of luteinization without rupture of the dominant ovarian follicle in rhesus monkeys treated with estradiol-17β on day 8 of the menstrual cycle

Previous results have established that 17β-estradiol (E₂) administered in capsules for 24 h on Day 6 of the menstrual cycle results in atresia of the dominant follicle (DF). The present experiment was designed to determine if atresia could be induced similarly as late as Day 8, when the DF is presumably larger, to facilitate biochemical analyses. On the morning of Day 8, laparoscopy was used to confirm the presence of the DF, and 4, 6, or 8 Silastic capsules containing E₂ were placed s.c. for 12 or 24 h. Treatment with E₂ for 12 h resulted in atresia of the dominant follicle: 2/4,4/5, and 2/5 with 4, 6, and 8 capsules, respectively. Increases in luteinizing hormone (LH) usually occurred following removal of E₂ after 12 h; similar increases resulted previously from treatment on Day 6, and are interpreted as the result of removal of E₂-induced negative feedback rather than an effect of positive feedback. In contrast to the efficacy of treatment for 12 h, treatment with E₂ for 24 h resulted in a lower incidence of atresia (2/5,1/6, and 1/4 with 4, 6, and 8 capsules), and premature LH surges were seen during treatment in almost all animals, especially with 6 or 8 capsules, initiating luteinization of the DF without ovulation. Regarding intrafollicular changes, E₂ treatment resulted in a 10-fold reduction in follicular fluid concentrations of estrogen, while progesterone (P) levels were augmented; the output of P by granulosa cells in culture was also enhanced by E₂ treatment. We conclude that the DF in monkeys remains susceptible to the atretogenic effects of E₂ as late as Day 8 of the cycle, but the amount of follicular material recoverable is not increased with the later treatment. Furthermore, the similarity between the luteinized unruptured follicles induced in this study and those occurring spontaneously in women suggests that this model may be valuable in elucidating the factors involved in this source of infertility in women. © 1994 Wiley-Liss, Inc.     

Effects of gender and phase of the menstrual cycle on the kinetics of ranitidine in healthy volunteers

The present study was undertaken to determine if differences exist in the pharmacokinetic parameters of oral ranitidine caused by gender and stage of the menstrual cycle. The study was performed in two steps, in the first a pharmacokinetic study was performed on 10 men (average age 35.5 yrs) and 10 women (average age 34.7 yrs) during the follicular phase, and in the second the pharmacokinetic study was performed only on the same women in their luteal phase. Subjects received a tablet dose of 300 mg ranitidine, and blood samples were drawn at several times after its ingestion. Plasma ranitidine concentration was determined by high performance liquid chromatography. Comparison of the pharmacokinetic parameters of women and men revealed statistically significant differences both in distribution volume (Vd) with values of 2.0 and 6.3 l/kg, Area Under Curve (AUC) with values of 7312.15 and 11471.94 ng/ml/h, and clearance (CLt) with values of 0.65 and 0.59 l/kg/h, respectively. Several pharmacokinetic parameters in women were different in the follicular compared to the luteal phase; for example, Vd was 2.0 and 5.6 l/kg, AUC was 7312.15 and 5195.83 ng/ml/h, and CLt was 0.65 and 0.97 l/kg/h, in the respective phases. Moreover, the maximum concentration (Cmax) was 1086 ng/ml in the follicular vs. 864 ng/ml in the luteal phase. The first study detected differences between men and women in several pharmacokinetic parameters, mainly those indicative of drug availability, for example, Vd, AUC, and CLt. Comparison of data obtained in the follicular phase with those obtained in the luteal phase revealed differences in most pharmacokinetic parameters, which is seemingly indicative of the characteristic physiological changes associated with the luteal phase that largely affect the kinetics and availability of drugs such as ranitidine. Although it has been postulated that hormonal fluctuation within the menstrual cycle phase is the primary cause of documented gender differences in the pharmacokinetics and pharmacodynamics of drugs, further study of related factors is required to fully understand how gender and menstrual cycle rhythms affect the pharmacokinetic process in their entirety.     

Endometrial tissue and plasma concentrations of 5-androstene-3 beta, 17 beta-diol during the menstrual cycle in normal premenopausal and perimenopausal women

A radioimmunoassay for 5-androstene-3 beta, 17 beta-diol (ADIOL) in human endometrium and plasma is described. The recognised criteria of reliability have been fulfilled. Plasma and endometrial tissue concentrations of ADIOL were determined in samples obtained from normal premenopausal and perimenopausal women (average ages 37 and 48 years respectively) at different phases of the menstrual cycle. In perimenopausal women plasma concentrations of ADIOL did not vary throughout the cycle (proliferative phase: 411 +/- 95 (SEM) pg/ml; secretory phase: 462 +/- 28.5 (SEM) pg/ml). For the premenopausal group the pattern was similar (proliferative phase: 568.4 +/- 56.9 (SEM) pg/ml; secretory phase: 663.1 +/- 64.7 (SEM) pg/ml) although a significant difference (P less than 0.05) was noted between late proliferative and late secretory phase levels in these women. A different pattern was observed for endometrial tissue concentrations of ADIOL. In both groups of women a significant (3-4-fold) increase occurred during the secretory phase. There was no apparent relationship between plasma and tissue concentrations of ADIOL either during the proliferative or the secretory phase. There was, however, an age associated decrease for both tissue and plasma ADIOL. Theories are proposed to account for the increase in ADIOL concentration during the luteal phase.     

Signet ring cells in fine needle aspiration cytology of breast carcinomas: review of the cytological findings in ten cases identified by histology

Objective:  To establish whether the presence of signet ring cells (SRCs) in histology sections of breast carcinoma cases was reflected by their presence in fine needle aspiration cytology (FNAC) smears, correlating to the histological type of breast carcinoma.
Methods:  We reviewed the FNAC findings of ten cases that had been diagnosed as primary breast carcinoma with SRCs on histological sections between 1998 and 2007. Slides and histological sections were obtained from the archives of Ege University Hospital.
Results:  FNA smears were reviewed for the following cytomorphological features: background, cellularity, architecture, nuclear pleomorphism and the presence of SRCs. The background was bloody in eight cases, necrotic in one, and clean in one. There was no mucinous material in any of the cases. Cellularity was prominent in five cases (hypercellular), moderate in three (cellular) and low in two (hypocellular). Loosely cohesive groups of tumour cells of varying size were observed in all cases. A plasmacytoid appearance to some of the tumour cells was seen in all cases and discohesive tumour cells were present in eight. Nuclear pleomorphism was high in six cases and moderate in four. SRCs were observed in seven of the ten cases. Two of these seven cases also had a tubular pattern and one had tumour giant cells.
Conclusions:  FNAC should be evaluated carefully regarding the presence of SRCs when cells with a plasmacytoid appearance are observed in either hyper- or hypocellular smears. The presence of single SRCs in FNACs with hypercellularity, high nuclear grade and tubular formation or tumour giant cells may be a clue in favour of ductal carcinoma. The presence of single SRCs in FNACs with hypocellularity and mild to moderate nuclear grade may be suggestive of lobular carcinoma. However, larger studies would be needed to establish the predictive value of the presence of SRCs on FNAC.     

Influence of the menstrual cycle and oral contraceptives on thermoregulatory responses to exercise in young women

Thermoregulatory responses to exercise in relation to the phase of the menstrual cycle were studied in ten women taking oral contraceptives (P) and in ten women not taking oral contraceptives (NP). Each subject was tested for maximal aerobic capacity ( ) and for 50% exercise in the follicular (F) and luteal (L) phases of the menstrual cycle. Since the oral contraceptives would have prevented ovulation a quasi-follicular phase (q-F) and a quasi-luteal phase (q-L) of the menstrual cycle were assumed for P subjects. Exercise was performed on a cycle ergometer at an ambient temperature of 24° C and relative air humidity of 50%. Rectal (T _re), mean skin ( ), mean body ( ) temperatures and heart rate (f _c) were measured. Sweat rate was estimated by the continuous measurement of relative humidity of air in a ventilated capsule placed on the chest, converted to absolute pressure (PH₂O_chest). Gain for sweating was calculated as a ratio of increase inPH₂O_chest to the appropriate increase inT _re for the whole period of sweating (G) and for unsteady-state (G_u) separately. The did not differ either between the groups of subjects or between the phases of the menstrual cycle. In P, rectal temperature threshold for sweating (T _{re, td}) was 37.85° C in q-L and 37.60° C in q-F (P < 0.01) and corresponded to a significant difference fromT _re at rest. TheT _re, andf _c increased similarly during exercise in q-F and q-L. No menstrual phase-related differences were observed either in the dynamics of sweating or in G. In NP,T _{re, td} was shorter in L than in F (37.70 vs 37.47° C,P<0.02) with a significantly greater value fromT _re at rest. The dynamics and G for sweating were also greater in L than in F. The G_u was 36.8 versus 16.6 kPa · ° C^–1 (P<0.01) while G was 6.4 versus 3.8 kPa · ° C^–1 (P<0.05), respectively. TheT _re, andf _c increased significantly more in phase F than in phase L. It was concluded that in these women performing moderate exercise, there was a greater temperature threshold and larger gains for sweating in phase L than in phase F. Intake of oral contraceptives reduced the differences in the gains for sweating making the thermoregulatory responses to exercise more uniform.     

Changes in the extracellular matrix of the normal human breast during the menstrual cycle

Summary The normal human mammary gland undergoes a well defined sequence of histological changes in both epithelial and stromal compartments during the menstrual cycle. Studies in vitro have suggested that the extracellular matrix surrounding the individual cells plays a central role in modulating a wide variety of cellular events, including proliferation, differentiation and gene expression. We therefore investigated the distribution of a number of extracellular matrix molecules in the normal breast during the menstrual cycle. By use of indirect immunofluorescence, with specific antibodies, we demonstrated that laminin, heparan sulphate proteoglycan, type IV collagen, type V collagen, chondroitin sulphate and fibronectin undergo changes in distribution during the menstrual cycle, whereas collagen types I, III, VI and VII remain unchanged. These changes were most marked in the basement membrane, sub-basement membrane zone and delimiting layer of fibroblasts surrounding the ductules where basement membrane markers such as laminin, heparan sulphate proteoglycan, and type IV and V collagens appear greatly reduced during the mid-cycle period (days 8 to 22). These results suggest that some extracellular matrix molecules may act as medittors in the hormonal control of the mammary gland, whereas others may have a predominantly structural role.     

CDK1 inhibition sensitizes normal cells to DNA damage in a cell cycle dependent manner

Cyclin-dependent kinase 1 (CDK1) orchestrates the transition from the G2 phase into mitosis and as cancer cells often display enhanced CDK1 activity, it has been proposed as a tumor specific anti-cancer target. Here we show that the effects of CDK1 inhibition are not restricted to tumor cells but can also reduce viability in non-cancer cells and sensitize them to radiation in a cell cycle dependent manner.

Radiosensitization by the specific CDK1 inhibitor, RO-3306, was determined by colony formation assays in three tumor lines (HeLa, T24, SQ20B) and three non-cancer lines (HFL1, MRC-5, RPE). Initial results showed that CDK1 inhibition radiosensitized tumor cells, but did not sensitize normal fibroblasts and epithelial cells in colony formation assays despite effective inhibition of CDK1 signaling. Further investigation showed that normal cells were less sensitive to CDK1 inhibition because they remained predominantly in G1 for a prolonged period when plated in colony formation assays. In contrast, inhibiting CDK1 a day after plating, when the cells were going through G2/M phase, reduced their clonogenic survival both with and without radiation. Our finding that inhibition of CDK1 can damage normal cells in a cell cycle dependent manner indicates that targeting CDK1 in cancer patients may lead to toxicity in normal proliferating cells. Furthermore, our finding that cell cycle progression becomes easily stalled in non-cancer cells under normal culture conditions has general implications for testing anti-cancer agents in these cells.