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Abstract Summary 77 SUMMARY This work was done to study the genotoxic effects of formaldehyde on the chromosomes of mice and the possible protective effect of vitamin C (L-ascorbic acid) against formaldehyde toxicity. As well as its pathological effects on liver, kidney, lung and spleen. The study was done in two experiments as follows: 1-1st experiment (acute exposure to formaldehyde): In this experiment, different doses of formaldehyde were injected intra-peritoneally into mice. Thirty-six mice were divided into six groups as following: 1-The first group was kept as a negative control (without any treatment). 2-The second group was given vitamin C 65.2 mg/kg B.wt. 3-The third group was given 20 mg/kg.B.wt. Equal to 1/10 LD50 of formaldehyde. 4-The fourth group was given 1/10 LD50 of formaldehyde in addition to 65.20 mg/kg B.wt.of vitamin C. 5-The fifth group was given 40 mg/kg.B.wt. Equal 1/5 LD50 of formaldehyde. 6-The sixth group was given 1/5LD50 of formaldehyde in addition to 65.20 mg/kg B.wt. of vitamin C. . After 24 hrs the same doses were injected to each group, half of the animal of each group were taken for cytogenetic studies after 48 hrs from Summary 78 the first injection. The other half (3 of each groups) were taken after 72 hrs from first injection. The effects of formaldehyde and formaldehyde with vitamin C on chromosome abnormalities and mitotic indices were examined. 2-2nd experiment (Chronic exposure to formaldehyde): In this experiment, different doses of formaldehyde were given orally. Sixty mice were divided in to six groups as following: 1-The first group was kept as a negative control (without any treatment). 2-The second group was kept as positive control receiving at a dose of 260.8 mg /kg.B.wt. vitamin C. 3-The third group was given formaldehyde at a dose of 2 mg/kg.B.wt. 4-The fourth group was given formaldehyde at a dose of 2 mg/kg.B.Wt in addition to 260.8 mg/kg.B.wt. vitamin C. 5-The fifth group was given formaldehyde at a dose of 4 mg/kg.B.wt. 6-The sixth group was given formaldehyde at a dose of 4 mg/kg.B.wt. In addition to 260.8 mg/kg B.wt. of vitamin C. All animals were sacrificed and samples were collected after 2 months from the beginning of the administration. The effects of formaldehyde and formaldehyde with vitamin C on chromosome abnormalities, mitotic indices were examined. Pathological effects of Summary 79 formaldehyde on liver, kidney, lung and spleen of mice were also evaluated. from the current study, the following results were obtained: 1-Acute treatment: -The acute treatment of formaldehyde induced significant effects (P 0.05) on chromosomal aberrations at a dose level of 1/10 and 1/5 LD50 for the two periods of treatment (48 and 72 hrs). At 48 hrs treatment, there was a significant difference in the number of aberrant cells between each of control group without treatment (26.33±2.72) and 65.2 mg/kg.B.wt. vitamin C control group (23.67±2.2), and groups treated with 1/10 LD50 and 1/5 LD50 of formaldehyde (51±0.57 and 55.67±2.08). - Mean ± SE of aberrant cells at 1/10 and 1/5 LD50 of formaldehyde for 72 hrs were 51.33±1.45 and 53±1.15. But it represented 31.33 ±0.3 in the control group without treatment and 29.67±0.88 in control with 65.2 mg/kg.B.wt. vitamin C. -There were different types of chromosomal aberrations appeared in the form of hypoploidy , gaps, fragments, chromatid deletion , chromatid break , centric fusion , centromeric attenuation, stickiness and ring chromosomes after 48 and 72 hrs. At 48 hrs, the most prominent type of chromosomal aberration at 1/10 LD50 of formaldehyde was fragments (11.00±2.08). However at 1/5 LD50 the most prominent types of chromosomal aberrations were fragments and chromosomal deletions, both measured (12.00±2.08 and 11.00±2.08). whereas, the lowest types of chromosomal aberrations at different types of treatments (1/10LD50 Summary 80 and 1/5 LD50 of formaldehyde ) were hypoploidy (2.67±0.67 and 3.33±0.33) , chromosomal gaps (1.33±0.88 and 2.33±1.20) and ring chromosomes ( 1.67±0.33 and 2.67±0.67) . -At 72 hrs groups the most prominent types of chromosomal aberrations of the group treated with 1/10 LD50 of formaldehyde were chromatid deletions and fragments (10.00±0.00 and 8.67±0.67). While the lowest type of chromosomal aberration in 1/10 LD50 of formaldehyde was gap (2.00±0.58). Also1/5 LD50 of formaldehyde the highest types of chromosomal aberrations were chromatid deletions and fragments (15.67±2.33 and 11.00±2.64). The lowest types of chromosomal aberrations in 1/5 LD50 of formaldehyde were gaps and rings chromosome both of them equal (2.00±0.58). ‐administration of vitamin C intra-peritoneal at a dose of 65.20 mg/kg B.wt. before the acute exposure to formaldehyde leading to decrease in the number of aberrant cells. At 48 hrs groups: Vitamin C induced significant reduction in number of aberrant cells in both 1/10 LD50 and 1/5LD50 of formaldehyde (28±2.64 and 8.33±4.41). Also 65.2 mg/kg.B.wt. vitamin C decreased levels of various types of chromosomal aberrations such as, at 1/10 LD50 of formaldehyde decreased fragments to (6.00±0.58). While at 1/5LD50 of formaldehyde both fragments and chromatid deletions decreased to (7.67±0.33). - At 72 hrs groups: vitamin C induced significant reduction in number of aberrant cells in both 1/10 LD50 and 1/5LD50 of formaldehyde (27±1.15 and 27.67±1.76). Also 65.2 mg/kg.B.wt. vitamin C decreased levels of various types of chromosomal aberrations, at which 1/10 LD50 Summary 81 of formaldehyde decreased chromatid deletions to (5.67±0.67). However at 1/5 LD50 of formaldehyde both fragments and chromatid deletions decreased to (6.00±1.15 and 6.67±1.20). -Chi square analysis for mitotic indices found there were a significant decrease in mitotic indices in groups treated by formaldehyde only such as 1/10 LD50 of formaldehyde and 1/5 LD50 of formaldehyde (3.17and 2.60). Highly significant difference were reported between 1/10 LD50 Formaldehyde and 1/10 LD50 Formaldehyde + 65.2 mg/kg.B.wt. vitamin C (3.17 and 5.63), and between 1/5 LD50 Formaldehyde 1/5 LD50 formaldehyde + 65.2 mg/kg.B.wt. vitamin C (2.60 and 5.57) in 48 hrs. Moreover, there were highly significant difference between 1/10 LD50 and 1/5 LD50 of formaldehyde treatments (2.93 and 2.53) and both of 1/10 LD50 formaldehyde + 65.2 mg/kg.B.wt. vitamin C and 1/5LD50 formaldehyde+ 65.2 mg/kg.B.wt. vitamin C (5.60 and 5.67) in 72 hrs groups. 2- Chronic treatment: The chronic treatment of formaldehyde induced significant effects (P 0.05) on chromosomal aberrations at a dose level of 2 mg/kg.B.wt. and 4 mg/kg.B.wt. -Mean±SE of aberrant cells at 2 and 4 mg/kg.B.wt. of formaldehyde for 2 months were high ( 37±0.71 and 47±0.71). However mean±SE for control equalled 22±0.71 in control without treatment and 27±0.71 for the group treated with 260.8 vitamin C. Summary 82 -There were different types of chromosomal aberrations, where the highest types of chromosomal aberrations in group treated by 2 mg/kg.B.wt. of formaldehyde were fragments and chromatid deletions (10±0.30 and 7.40±0.81). also in 4 mg/kg.B.wt. of formaldehyde the most prominent types were fragments and chromatid deletions at frequency (14.40±1.50 and 13.60±1.20), and the lowest type of chromosomal aberration in 2 mg/kg.B.wt. and 4 mg/kg.B.wt. of formaldehyde treatments was gaps (0.60±0.40 and 3.00±0.32). -Administration of vitamin C orally at a dose of 260.8 mg/kg B.wt. with the formaldehyde leading to decreased in the number of aberrant cells. vitamin C induced significant reduction in number of aberrant cells in both 2 mg/kg.B.wt. and 4 mg/kg.B.wt. of formaldehyde (32±0.71 and 42±0.71),furthermore the addition of 260.8 mg/kg.B.wt. vit. C induced significant reduction of various types of chromosomal aberrations such as , at 2 mg/kg.B.wt. of formaldehyde fragments and chromatid deletions decreased to (7.4±1.75 and 6.00±1.00) . While at 4 mg/kg.B.wt. of formaldehyde fragments , chromatid deletions, sticknesses and centric fusions decreased to (6.6±0.98, 6.0±0.84 , 4.60±0.51 and 4.20±0.49 respectively ). -Chi square analysis for mitotic indices indicated that, there was there was a significant decrease in mitotic indices in group treated by 2mg/kg.B.wt. and 4 mg/kg.B.wt. of formaldehyde (6.82 and 4.46) than control group without treatment (7.67) and 260.8 mg/kg.B.wt. vitamin C control group (7.96). Addition of vitamin C in groups 2 mg/kg.B.wt. and 4 mg/kg.B.wt. increased the mitotic indices to (7.16 and 6.88). Summary 83 ‐The histopathological examination of treated mice liver with 2 and 4 mg/kg.B.wt. of formaldehyde for 2 months. It revealed diffuse hepatic degenerative changes in the form of cytoplasmic vaculation, coagulative necrosis and hyperplasia of bile duct. The examined kidney showed perivascular inflammatory cellular infiltration, congestion, vacuolar and hyDROPic degeneration. The examined lung showed multiple lymphocytic cellular infiltration with desquamation of the bronical lining epithelium. The examined spleen of rats showed lymphoid depletion, in addition to splenic hemosiderosis . -The additions of vitamin C to formaldehyde decreased the pathological lesions of the liver, kidney, lung and spleen of mice. |