Effects of age, gender, folate and vitamin B[12] satus on DNA Damage

A number of host risk factors affecting back ground rates of chromosomal damage in peripheral blood lymphocytes was undertaken into a view to aid in the evaluation of these factors. To determine the effect of age, gender, smoking, vitamin B[12] and folic acid serum level on DNA damage as measured by micronucleus frequency in peripheral blood lymphocytes. Followed by an intervention study to determine whether supplementation with folic acid and vitamin B[12] could alter the micronucleus index. Cytokinesis block micronucleus [CBMN] technique was perftrmed on 36 healthy volunteers; 17 males [mean age 43.47years] of them 19.4% smokers and 19 females [mean age 45 years]. The effect of the studied factors on base line level of MN was evaluated. The dietary intervention involve supplementation with a daily dose of 2000 micro g folic acid and 25 micro g vitamin B[12] [10 times RDI] over a period of 2 months. The study showed that: [i] The frequency of micronuclei was positively correlated with age [r=0.809, P=0.00] and that the correlation was more pronounced among females [r=0.842, P=0.00] than males [r=0.800, P=0.00]. [ii] Gender has no effect on MN frequency [P=0.287], as well as smoking [P 0.185]. [iii] MN frequency was negatively correlated with serum folic acid [r=-0.469, P=0.004], and serum vitamin B[12] [r=-0.590, P 0.00]. After vitamin supplementation MN frequency was significantly reduced [P=0.00], this reduction was more. significant in persons with high initial MN frequency [r=-0.531, P=0.001], and was significantly negatively correlated with serum vitamin B[12] [r=-0.480, P=0.003] and serum folic acid [r=-0.345, P=0.039]. [i] There is an age related increase in MN frequency [ii] Supplementation with 2000 micro g folic acid and 25 micro g vitamin B[12] in tablets is sufficient to minimize MN frequency. Thus it appears that dietary intake above the RDI of these vitamins could be of particular importance in genomic stability, for which ageing is a contributing factor

Disease associated balanced chromosome rearrangements-report on 12 cases

The population frequency of familial disease balanced chromosome rearrangement with discordance for an abnormal phenotype is unknown. De novo balanced chromosome rearrangements are present in approximately 1:2000 newborn. The increased frequency of associated diseases may be due to truncation, inactivation or overexpression of specific genes. Uniparental disomy [UPD] has also been implicated. We report on 12 cases with apparently balanced chromosome rearrangements with abnormal phenotypes, 8 familial [5 families] and 4 de novo. Maternal inheritance accounted for 7/8 cases. The rearrangements included reciprocal translations in 8 cases, Robertsonian translocation in 2 cases and pericentric inversion in 2 cases. Apparently balanced rearrangements in general, represent an interpretational and counseling dilemma when detected in cases with abnormal phenotypes and/or mental retardation

Evaluation of genetic damage in human lymphocytes of women using oral contraceptives

The genotoxic effect of low dose oral contraceptive pills on the frequency of chromosomal aberrations [CA] and sister chromatid exchange [SCE] was investigated on 43 healthy females classified as; 15 women received pills containing 150 microg desogesterel and 30 microg ethinyl estradiol, 14 women received pills containing 250 microg Norgestamine and 35 microg ethinyl estradiol and 14 women received pills containing 75 microg gestodene and 30 microg ethinyl estradiol. The pills were taken orally as a single daily usage in a monthly cycle of 3 weeks and one week off during twelve consecutive menstrual cycles. Also 15 healthy women with regular menstrual cycle not receiving any hormonal therapy were included as a control. There was no statistically significant difference in CA, SCE when healthy women were compared with women taking oral contraceptive pills [p>0.05]. Also no statistically significant difference was detected when comparing between the 3 different types of oral contraceptives [p>0.05]. Our data suggest that the 3 types of oral contraceptive pills used during twelve consecutive menstrual cycles do not induce chromosomal aberrations or sister chromatid exchange in peripheral blood lymphocytes of women

BRCA1 [l85 del AG] mutation among Egyptian breast cancer female patients

This study was conducted to estimate the frequency of BRCA1 [1 85delAG] mutation among Egyptian female patients with breast cancer. Forty selected female patients with breast cancer, 80 of their female relatives and 10 healthy females as a control group were included in this study. Result: The age of onset of breast cancer was below 40 years in 25 [62.5%] patients and above 40 years in 15 [37.5%] patients.There were significant differences among the patients regarding the age at menarche before 13 years [P=0.011, P<0.05], onset of breast cancer [P=0.000, P<0.001], parity [P=0.000, P<0.001], first delivery before 30 years of age [P=0.04, P<0.05], breast feeding [P=0.002, P<0.05], and positive family history [P=0.000, P<0.001]. The frequency of BRCA1 [1 85delAG] mutation was found among 10% of the patients group .Eight percent of patients with early onset below 40 years and 13.5% of patients with onset after 40 years were heterozygotes for the mutation. Three percent of patients with unilateral breast cancer, 40% of patients with bilateral breast cancer and 50% of patients with breast ovarian cancer were carrying the mutation. Our results indicated that breast ovarian cancer and bilateral breast cancer patients were likely to have BRCA1 [l85delAG] mutation than in unilateral breast cancer