The COVID-19 vaccine acceptance in Jordan: a meta-analysis and review of the literature.

OBJECTIVE: The COVID-19 pandemic continues to impose a health and economic burden on the global population with millions of deaths linked to infection with the virus. Vaccination remains the most effective intervention to reduce infection, severity, and hospitalization for COVID-19. However, vaccine hesitancy has emerged as a global phenomenon facing the effective implementation of coronavirus vaccination programs. Several studies have been conducted in Jordan to examine vaccine acceptability. This study aims at calculating the pooled acceptance rate for the COVID-19 vaccine in Jordan. MATERIALS AND METHODS: The Systematic Reviews and Meta-Analysis (PRISMA) guideline was adopted to conduct the present meta-analysis. The RevMan software was utilized to estimate the poled acceptance rate and to construct the study Figures. RESULTS: Data from 22 studies that fit the study inclusion criteria were included in the analysis. The total number of participants was 38,600. The pooled COVID-19 vaccine acceptance rate was estimated to be 39.89% [95%-CI: 33.52-46.27]. Subgroup analysis, according to the year of publication, showed a pooled COVID-19 vaccine acceptance rate of 36.70% [95%-CI: 29.27-44.12, I2=100%, p<0.0001) for 2021, and 48.90% [95%-CI: 40.21-57.65, I2=91.0%, p<0.0001) for 2022. This indicates about a 33% increase in vaccine acceptance through 2022. CONCLUSIONS: The reported COVID-19 vaccine acceptance rate in Jordan is below expectations. While the acceptance rate has increased in 2022 compared to 2021, there is still a need for more efforts and awareness interventions to reach a convincing level of vaccination against COVID-19 in Jordan.

The impact of multiple blood donations on the risk of cardiovascular diseases: Insight of lipid profile.

OBJECTIVES: The reduction in blood viscosity and iron store were proposed to be connected to the reduction in the risk of cardiovascular disease (CVD) among multiple blood donors. Herein, we evaluated the modulation of serum lipids levels in accordance with donation events. Furthermore, atherogenic impacts on the risk of CVD were investigated. MATERIALS AND METHODS: A total of 100 voluntarily male donors were included in the study. Fifty donors were multiple time donors (MTD) and 50 were single time donors (STD). Levels of serum lipids were determined and atherogenic indices including TG/HDL and CHO/HDL ratios were calculated. QRISK2 parameters were determined to evaluate the 10-years risk of developing CVD. RESULTS: Among MTD, there were significantly higher serum levels of triglycerides (TG) and very low-density lipoproteins (VLDL) combined with significantly lower HDL level. These modulations were significantly correlated to the extent of donation. Both CHO/HDL and TG/HDL ratios were also significantly higher among MTD. However, only TG/HDL ratio was strongly correlated to the donation extent even when controlled for age, BMI and smoking status. Despite the significant difference in QRISK2 parameters between study groups, none of these parameters was correlated to the extent of donation when controlling for age, BMI and smoking status. CONCLUSION: We demonstrate that multiple blood donation is associated with an unfavorable modulation of serum levels of lipids that is influenced by donation extent. This modulation is not associated with an increased risk of CVD but may weakly contribute in a higher risk for coronary heart disease (CHD).

Assessment of genotoxicity of vincristine, vinblastine and vinorelbine in human cultured lymphocytes: a comparative study.

Vincristine (VCR), vinblastine (VBL) and vinorelbine (VRL) are anticancer agents from the Vinca alkaloid family that have the potential to induce genotoxic effect. The aim of the present study was to compare the genotoxic effect of VCR, VBL and VRL. Levels of 8-hydroxy-2-deoxy guanosine (8-OHdG) and sister chromatid exchanges (SCEs) were measured in cultured human blood lymphocytes treated with VCR, VBL and VRL at concentrations of 0.01 and 0.1 µg/mL. Results showed that VCR, VBL and VRL significantly increased the 8-OHdG levels (p <0.05), whereas it did not cause a significant increase in the frequencies of SCEs in human blood lymphocytes as compared to controls. On the other hand, all three agents significantly increased cells mitotic index (p <0.05). At both tested concentrations, the magnitude of the increase in 8-OHdG was VBL>VCR>VRL. In conclusion, VCR, VBL and VRL induce DNA damage as indicated by the increase in the 8-OHdG biomarker but with different magnitude.

Screening for mutations in RPGR and RP2 genes in Jordanian families with X-linked retinitis pigmentosa.

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous disease causing progressive degeneration of retinal photoreceptor cells. X-linked RP (XLRP), in which photoreceptor degeneration begins in early childhood and complete blindness often occurs by the fourth decade of life, constitutes the most severe form of this disease. Two genes commonly associated with XLRP have previously been cloned: retinitis pigmentosa GTPase regulator (RPGR) and retinitis pigmentosa 2 (RP2). We sought to identify mutations in these genes in Jordanian families suffering from this disease. Five unrelated Jordanian families with confirmed XLRP were screened for such mutations using direct sequencing. Three mutations were identified in the ORF15 exon of RPGR. The silent g.ORF15+470G>A substitution and the g.ORF15+1822insA insertion in the 3ꞌ-untranslated region were found in both normal and affected male family members at comparable frequencies, and thus were considered normal variants. The third mutation, g.ORF15+588G>A, in which alanine is substituted by threonine, was found in all affected men and one unaffected man in the two families harboring this variant. Thus, this mutation may be pathogenic, but with incomplete penetrance. No RP2 mutations were found among the examined families. Mutation screening of RP patients is essential to understand the mechanism behind this disease and develop treatments. A complete family history is required to identify its inheritance pattern and provide genetic counseling for patients and their families.

Assessment of genotoxicity of waterpipe smoking using 8-OHdG biomarker.

Waterpipe tobacco smoking is increasing in popularity, particularly among young adults. This popularity is related to the lack knowledge regarding the health effects of waterpipe smoking. In this study, we examined the genotoxicity of waterpipe smoking using an 8-hydroxy deoxyguanosine (8-OHdG) assay. Genotoxicity was evaluated in the saliva, urine, and serum of 66 waterpipe adult smokers and 46 healthy nonsmokers. The level of addiction to waterpipe smoking was evaluated using the Lebanon Waterpipe Dependence Scale-11. Levels of 8-OHdG in the samples were measured using commercially available enzyme-linked immunosorbent assays. Levels of 8-OHdG in the saliva (52,430 ± 2923 vs 48,430 ± 4189 pg/mL), urine (2815 ± 312 vs 2608 ± 180 pg/mL), and serum (19,720 ± 202 vs 19,670 ± 254 pg/mL) were similar between waterpipe smokers and nonsmokers (P > 0.05). In addition, no correlations were found between dependence score and levels of 8-OHdG in all sample types. In conclusion, 8-OHdG is not a good biomarker for genotoxic effect of waterpipe smoking.

Fresh pomegranate juice ameliorates insulin resistance, enhances ß-cell function, and decreases fasting serum glucose in type 2 diabetic patients.

Although the effects of pomegranate juice (PJ) on type 2 diabetic (T2D) conditions have been reported, a clinical study focusing on the short-term effects on different diabetic variables is still needed. We hypothesized that PJ consumption by T2D patients could reduce their insulin-resistant state and decrease their fasting serum glucose (FSG) levels, 3 hours after juice ingestion. This study demonstrated the direct effect of fresh PJ on FSG and insulin levels in T2D patients. Blood samples from 85 participants with type 2 diabetes were collected after a 12-hour fast, then 1 and 3 hours after administration of 1.5 mL of PJ, per kg body weight. Serum glucose was measured based on standard methods using the BS-200 Chemistry Analyzer (Shenzhen Mindray Bio-Medical Electronics Co Ltd, Shenzhen, China). Commercially available immunoassay kits were used to measure human insulin. Generally, the results demonstrated decreased FSG, increased ß-cell function, and decreased insulin resistance among T2D participants, 3 hours after PJ administration (P < .05). This hypoglycemic response depended on initial FSG levels, as participants with lower FSG levels (7.1-8.7 mmol/L) demonstrated a greater hypoglycemic response (P < .05) compared with those who had higher FSG levels (8.8-15.8 mmol/L). The effect of PJ was also not affected by the sex of the patient and was less potent in elderly patients. In conclusion, this work offers some encouragement for T2D patients regarding PJ consumption as an additional contribution to control glucose levels.

The role of TNF-α G-308A promoter polymorphism in glycemic control in Type 2 diabetes patients.

BACKGROUND: TNF-α polymorphisms were shown to be associated with insulin resistance and diabetes development and complications. AIM: To investigate the association between glycemic control in Type 2 diabetes patients and TNF-α G-308A single nucleotide polymorphism (SNP). METHODS: This was a cross-sectional observational study, where diabetes patients from both genders (170 male and 185 female) were enrolled in the study. Patients were divided into two groups: good glycemic control (n = 158) and poor glycemic control (n = 197). Genotyping of TNF-α G-308A SNP was carried out using restriction fragment length polymorphisms-polymerase chain reaction. RESULTS: The results showed that TNF-α G-308A SNP is strongly associated with glycemic control in type 2 diabetes patients. Patients with the AA and AG genotypes had better glycemic control than those with GG genotype (P < 0.01). Other parameters that impacted glycemic control include duration of the disease (P < 0.01) and response to insulin therapy (P < 0.01). However, no contribution for gender or statins use to glycemic control was observed (P > 0.05). CONCLUSION: TNF-α G-308A SNP might modulate glycemic control among type 2 diabetes patients.

Diabetes impairs synaptic plasticity in the superior cervical ganglion: possible role for BDNF and oxidative stress.

The majority of diabetics develop serious disorders of the autonomic nervous system; however, there is no clear understanding on the causes of these complications. In this study, we examined the effect of streptozocin (STZ)-induced diabetes on activity-dependent synaptic plasticity, associated levels of brain-derived neurotrophic factor (BDNF) and antioxidant biomarkers in the rat sympathetic superior cervical ganglion. Diabetes (STZ-induced) was achieved by a single intraperitoneal injection of streptozocin (55 mg/kg).Compound action potentials were recorded from isolated ganglia before (basal) and after repetitive stimulation, or trains of paired pulses to express ganglionic long-term potentiation (gLTP) or long-term depression (gLTD). The input/output curves of ganglia from STZ-treated animals showed a marked rightward shift along most stimulus intensities, compared to those of ganglia from control animals, indicating impaired basal synaptic transmission in ganglia from STZ-induced diabetic animals. Repetitive stimulation induced robust gLTP and gLTD in ganglia isolated from control animals; the same protocols failed to induce gLTP or gLTD in ganglia from STZ-induced diabetic animals, indicating impairment of activity-dependent synaptic plasticity in these animals. Molecular analysis revealed significant reduction in the levels of BDNF and the ratio of glutathione/oxidized glutathione. Additionally, the activity of glutathione peroxidase, glutathione reductase, catalase, and the levels of thiobarbituric acid-reactive substances were increased in ganglia from STZ-treated animals. In conclusion, impaired basal synaptic transmission and synaptic plasticity are associated with reduced BDNF and altered oxidative stress biomarkers in the sympathetic ganglia from STZ-induced diabetic animals, suggesting a possible correlation of these factors with the manifestations of STZ-induced diabetes in the peripheral nervous system.

Frequency of MDR1 single nucleotide polymorphisms in a Jordanian population, including a novel variant.

The multidrug resistance gene (MDR1 or ABCB1) codes for P-glycoprotein, which plays an important role in regulating absorption, distribution, and elimination of drugs. We examined MDR1 gene variants in 100 unrelated subjects from various regions of Jordan. The MDR1 gene was scanned using direct sequencing. Six rare variants in MDR1 were detected, including a new variant, T3075A. This variant did not affect the protein sequence (synonym for threonine). Among the common SNPs, the frequencies of rs1128503 (C1236T) genotypes were: 0.23 (CC), 0.41 (CT) and 0.36 (TT). For the rs2032582 (G2677T) SNP, genotype frequencies were 0.38 for GG, 0.45 for GT, 0.13 for TT, 0.03 for GA, and 0.01 for TA, whereas for rs1045642 (C3435T), genotype frequencies were 0.17 for CC, 0.5 for CT and 0.33 for TT. The observed distribution of the common variants in the Jordanian population was within the range detected in other populations. These data on MDR1 gene variants in the Jordanian population will be useful for investigations on response to P-glycoprotein substrate drugs.

The role of type II deiodinase polymorphisms in clinical management of hypothyroid patients treated with levothyroxine.

STUDY OBJECTIVE: Several factors can affect achieving the goals with levothyroxine (L-T4) therapy. This study investigates the clinical and biochemical response to L-T4 replacement therapy in hypothyroid patients in correlation with genetic variation in Deiodinase type || (DIO2) gene. DESIGN AND SETTING: This is a cross-sectional correlation study. The setting was the diabetes and endocrinology clinics at 2 Jordanian Hospitals. METHODOLOGY: Patients with primary hypothyroidism who are controlled on stable L-T4 replacement therapy were recruited and thyroid function test was performed. Genetic analysis to detect 4 single nucleotide polymorphisms (SNPs) rs225011, rs7140952, rs225012 and rs2839858 in DIO2 gene was carried out using the polymerase chain reaction-based restriction fragment length polymorphism assay (PCR-RFLP). RESULTS: There was no correlation between the 4 SNPs in DIO2 gene and replacement doses of L-T4, whereas a statistical significance was found between rs7140952 and central obesity (P<0.05), and systolic and diastolic blood pressure (P<0.05). The dose of L-T4 was associated with lower levels of TSH, fT4, central obesity, body mass index and waist circumference. CONCLUSION: While L-T4 dose is associated with several positive effects on hypothyroid patients, none of the examined SNPs in DIO2 is correlated with replacement doses of the drug. However, rs7140952 polymorphism is associated with components of metabolic syndrome including blood pressure and central obesity.

Caffeine prevents cognitive impairment induced by chronic psychosocial stress and/or high fat-high carbohydrate diet.

Caffeine alleviates cognitive impairment associated with a variety of health conditions. In this study, we examined the effect of caffeine treatment on chronic stress- and/or high fat-high carbohydrate Western diet (WD)-induced impairment of learning and memory in rats. Chronic psychosocial stress, WD and caffeine (0.3 g/L in drinking water) were simultaneously administered for 3 months to adult male Wistar rats. At the conclusion of the 3 months, and while the previous treatments continued, rats were tested in the radial arm water maze (RAWM) for learning, short-term and long-term memory. This procedure was applied on a daily basis to all animals for 5 consecutive days or until the animal reaches days to criterion (DTC) in the 12th learning trial and memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Chronic stress and/or WD groups caused impaired learning, which was prevented by chronic caffeine administration. In the memory tests, chronic caffeine administration also prevented memory impairment during chronic stress conditions and/or WD. Furthermore, DTC value for caffeine treated stress, WD, and stress/WD groups indicated that caffeine normalizes memory impairment in these groups. These results showed that chronic caffeine administration prevented stress and/or WD-induced impairment of spatial learning and memory.

Association between polymorphisms in erythropoietin gene and upper limit haematocrit levels among regular blood donors.

PURPOSE OF THE STUDY: Erythropoietin (EPO) is a glycoprotein hormone that functions primarily on the stimulation and control of erythropoiesis in bone marrow. In this study, polymorphisms in EPO gene; C3434T, G3544T (rs551238) and rs1617640 were evaluated to determine their frequencies and genotype distribution patterns among blood donors with upper-limit haematocrit level. SUBJECTS AND METHODS: A total of 298 subjects, 181 blood donors with haematocrit level greater or equal to 48% and 117 donors with haematocrit between 42-47.5% as control were recruited. All subjects were genotyped for C3434T, rs551238 polymorphisms and for rs1617640 using restriction fragment length polymorphism method (PCR-RFLP) and sequencing techniques. RESULTS: A significant difference was found in rs1617640 and rs551238 genotype frequencies in blood donors with upper-haematocrit compared to the control group (P<0.05). In accordance with genotype frequencies, G allele in these two polymorphisms were found at higher frequency among upper-haematocrit group compared to the control (P<0.05). On the other hand, C3434T polymorphism was not significantly different between the two groups, neither for genotype frequencies nor for allele frequencies. CONCLUSION: Results suggest a strong association between rs551238 and rs1617640 polymorphisms in the EPO gene and upper-limit haematocrit level among blood donors.

Waterpipe tobacco and cigarette smoking among university students in Jordan.

SETTING: While waterpipe and cigarette smoking have been well studied in Syria and Lebanon, data from Jordan are limited. OBJECTIVES: To characterize the relative prevalence of waterpipe tobacco and cigarette smoking among university students in Jordan, and to compare the demographic and environmental factors associated with each form of tobacco use. DESIGN: We surveyed 1845 students randomly recruited from four universities in Jordan. We used multivariable logistic regression controlling for clustering of individuals within universities to determine associations between demographic and environmental covariates and waterpipe tobacco and cigarette use. RESULTS: Waterpipe tobacco smoking rates were 30% in the past 30 days and 56% ever, while cigarette smoking rates were 29% in the past 30 days and 57% ever. Past 30-day waterpipe tobacco smoking rates were 59% for males and 13% for females. Females had substantially lower odds than males of being current waterpipe (OR 0.12, 95%CI 0.10-0.15) or cigarette (OR 0.08, 95%CI 0.05-0.14) smokers. Current cigarette smoking was more significantly associated with markers of high socio-economic status (SES) than waterpipe tobacco smoking. CONCLUSION: Waterpipe tobacco smoking is as common as cigarette smoking among Jordanian university students. While cigarette smoking is consistently associated with high SES, waterpipe tobacco smoking is more evenly distributed across various populations.

Correlation of plasma resistin with obesity and insulin resistance in type 2 diabetic patients.

AIM: The aim of this case-control study was to assess the relationship between resistin levels and obesity and insulin resistance in type 2 diabetic patients. METHODS: The study involved a sample of the Jordanian population that included 140 type 2 diabetic patients and 125 control subjects. RESULTS: Serum resistin levels were higher in type 2 diabetic patients compared with the controls (P<0.01). Markers of adiposity [body mass index (BMI) and waist circumference (WC)] and insulin resistance, as well as fasting blood glucose, glycated haemoglobin, urea and blood pressure were considerably higher among the studied diabetics than in the controls. When diabetic patients were subdivided into age-group categories of 10-year intervals, resistin levels significantly increased with increased age, with a significant proportion in the group aged>60 years (P<0.01). Similarly, there was a significant association between plasma resistin and blood urea with growing older in diabetic patients. Pearson's analysis revealed positive correlations between plasma resistin and age, urea, creatinine, insulin, BMI, WC, body-fat content and homoeostasis model assessment (HOMA). Furthermore, plasma resistin concentrations were higher in type 2 diabetic obese patients than in non-diabetic obese subjects (P<0.01), whereas no such difference was found between overweight and normal-weight controls. CONCLUSION: These results suggest that variations in resistin concentrations are not directly related to susceptibility to type 2 diabetes. However, it may be that resistin plays a role in the pathogenesis of obesity and insulin resistance, both of which could, indirectly, contribute to the development of type 2 diabetes.

Association of longevity with IL-10 -1082 G/A and TNF-alpha-308 G/A polymorphisms.

Cytokines are crucial for the regulation of inflammation development in humans. Many studies have shown that variations in cytokine genes might play a role in determining human longevity. This study examined the changes in the gene pool relevant to the -308 G/A polymorphism in the promoter region of the proinflammatory cytokine tumour necrosis factor (TNF)-alpha gene and the -1082 G/A polymorphism in the promoter region of anti-inflammatory cytokine interleukin (IL)-10 gene with aging and survival selection occurs in the Jordanian population. IL-10 -1028 G/A and TNF-alpha-308 G/A were genotyped in 119 randomly selected elderly subjects (41 women and 78 men) with a mean age of 90.2 years and young control subjects of 118 (46 women and 72 men) with a mean age of 31.9 years. No significant differences were found in the genotype and allele frequencies of TNF-alpha gene variants between the two groups (P > 0.05) while the IL-10 genotype and allele frequencies were significantly associated with longevity in men (P < 0.05) but not in women (P < 0.05). Thus, IL-10 -1028 G/A polymorphism seems to play a role in the pathway to longevity in Jordanian men.

Missense mutation of the EDA gene in a Jordanian family with X-linked hypohidrotic ectodermal dysplasia: phenotypic appearance and speech problems.

Mutations in the EDA gene are responsible for X-linked hypohidrotic ectodermal dysplasia, the most common form of ectodermal dysplasia. Males show a severe form of this disease, while females often manifest mild to moderate symptoms. We identified a missense mutation (c.463C>T) in the EDA gene in a Jordanian family, using direct DNA sequencing. This mutation leads to an amino acid change of arginine to cysteine in the extracellular domain of ectodysplasin-A, a protein encoded by the EDA gene. The phenotype of a severely affected 11-year-old boy with this mutation included heat intolerance, sparse hair (hypotrichosis), absence of 17 teeth (oligodontia), speech problems, and damaged eccrine glands, resulting in reduced sweating (anhidrosis). Both the mother (40 years old) and the sister (10 years old) were carriers with mild to moderate symptoms of this disease, while the father was healthy. This detailed description of the phenotype caused by this missense mutation could be useful for prenatal diagnosis.

Adverse effect of combination of chronic psychosocial stress and high fat diet on hippocampus-dependent memory in rats.

The combined effects of high fat diet (HFD) and chronic stress on the hippocampus-dependent spatial learning and memory were studied in rats using the radial arm water maze (RAWM). Chronic psychosocial stress and/or HFD were simultaneously administered for 3 months to young adult male Wister rats. In the RAWM, rats were subjected to 12 learning trials as well as short-term and long-term memory tests. This procedure was applied on a daily basis until the animal reaches days to criterion (DTC) in the 12th learning trial and in memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Groups were compared based on the number of errors per trial or test as well as on the DTC. Chronic stress, HFD and chronic stress/HFD animal groups showed impaired learning as indicated by committing significantly (P<0.05) more errors than untreated control group in trials 6 through 9 of day 4. In memory tests, chronic stress, HFD and chronic stress/HFD groups showed significantly impaired performance compared to control group. Additionally, the stress/HFD was the only group that showed significantly impaired performance in memory tests on the 5th training day, suggesting more severe memory impairment in that group. Furthermore, DTC value for above groups indicated that chronic stress or HFD, alone, resulted in a mild impairment of spatial memory, but the combination of chronic stress and HFD resulted in a more severe and long-lasting memory impairment. The data indicated that the combination of stress and HFD produced more deleterious effects on hippocampal cognitive function than either chronic stress or HFD alone.

The effect of trifluoperazine on the genotoxicity of bleomycin in cultured human lymphocytes.

The effects of trifluoperazine on the toxicity and mutagenicity of bleomycin were examined in cultured human lymphocytes. Lymphocyte cultures were initiated from three adult healthy non-smoking male volunteers. Cultures were exposed to the drugs for either three or twenty hours prior to cell collection. The toxic and clastogenic effects of the different treatments were represented by the reduction in the mitotic indices and the induction of chromosomal aberrations (CA) respectively. Both TFP and BLM significantly increased CA frequencies and reduced the mitotic indices (MI) following all treatments. The reduction in the mitotic indices and the increase in CA frequencies induced by the combined administration of both BLM and TFP were highly significant (p < or = 0.001), but they were not significantly different from the sum of those induced by the separate treatments with the two drugs. These combined treatments, however, potentiated the odds ratios compared to those of the separate drug treatments. Therefore, though the effect of TFP on the clastogenic and cytotoxic effects of BLM was additive, the observed potentiation of the odds ratios of the combined treatments compared to those of the separate treatments suggested a significant enhancement in the expected chemotherapeutic effects of BLM when administered with TFP.

The mutagenic and toxic effects of bleomycin and trifluoperazine in Drosophila melanogaster.

The mutagenic and toxic effects of trifluoperazine and bleomycin on Drosophila were investigated in the progenies of males injected with 0.2 microliter of bleomycin and/or trifluoperazine. The Muller-5 method was used to study the induction of complete- and mosaic-sex-linked recessive lethals induced by 0.1 microgram/ml bleomycin and/or 0.1 mM trifluoperazine in the five successive broods, mainly representing the different stages of spermatogenesis. Trifluoperazine increased the induction rate of sex-linked recessive mutations above the spontaneous rates of the control, but these increases were not statistically significant at the 5% level27 in any of the five different broods. Contrary to trifluoperazine, bleomycin significantly (5% level)27 increased the induction rate of the complete sex-linked recessive lethals over those of the control in the meiotic and premeiotic broods C and D, and the meiotic brood E. As with the separate treatment with bleomycin, the frequencies of the complete sex-linked recessive lethals induced by the simultaneous combination treatment of 0.1 microgram/ml bleomycin and 0.1 mM trifluoperazine were significantly higher than those of the control at the 5%27 level, only in the meiotic and premeiotic broods, but they were not significantly higher than those induced by bleomycin treatment alone19. Treatments with 0.1 mM trifluoperazine enhanced the toxicity, sterility and the number of mutated clusters induced by 0.1 mM bleomycin but did not significantly increase the rates of induced lethals over the additive effects of both drugs in the meiotic and premeiotic stages, suggesting no potentiation effects for trifluoperazine over those of bleomycin in Drosophila. Higher concentrations of the two drugs could not be used due to their high toxicity and sterility effects.

Induction of mosaic sex-linked recessive lethals in the different germ cell stages of Drosophila melanogaster by bleomycin.

The mutagenicity of bleomycin was studied in the different stages of spermatogenesis in Drosophila melanogaster. Following the injection of 2 microliters of 0.1 micrograms/ml of the chemical into young wild-type males, complete and mosaic sex-linked recessive lethals were scored by the Muller-5 method in five successive broods, mainly representing the different stages of spermatogenesis. The delayed mutagenic effect of the chemical was measured by the proportion of mosaic progeny produced. The results showed that bleomycin significantly increased the proportions of both complete and mosaic lethals in the broods representing the meiotic and pre-meiotic stages, but did not show any significant increase in these proportions in the broods representing the sperms and spermatids. The sizes of the mutated areas in the F1 gonads represented by the proportions of lethal-bearing females in F2 mosaic cultures were small, indicating that the genetic instabilities induced by bleomycin were transformed into actual mutations in later zygotic divisions. The significant divisions. The significant production of mosaic progeny in the F4 generation of the treated males showed that the mosaic F1 females produced by bleomycin were able to produce further mosaic progeny and suggested that bleomycin-induced instabilities can be transmitted as such for many future generations.