الفهرس 
Chapter I : IntroductionOnly 14 pages are availabe for public view
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Abstract
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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
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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
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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
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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
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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.
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-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).
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‐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.