الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
The work was planned to study the effect of benzo(a)pyrene
on pregnant rats and their fetuses .
In the first experiment the pregnant rats administered B(a)P on
three doses 12.5 , 50 and 100 mg/kg at 8th , 12th and from 8th to the
12th day of gestation. Rats in all groups were kept under observation till
the 20th day of gestation at which they were sacrificed under ether
anesthesia. Fetuses were removed from the uterus and evaluated for
mortality rate, fetal development through morphological, visceral and
growth retardation. External and skeletal malformations and histological
changes of liver were examined. This experiment contains five groups.
The first group contains 9 pregnant rats reserved distal water and used as
negative control. Other four major groups of pregnant rats each of 27
animals were divided into three subgroups. Benzo[a]pyrene was
dissolved in corn oil and orally administered at doses 12.5 , 50 and 100
mg/kg b. wt. for the pregnant rats at 8th , 12th (single dose) and from 8th
to 12th day of gestation (repeated dose).
Group (2): Pregnant animals were received corn oil (10 ml/ kg. b. wt) at
8th ,12th and from 8th to 12th day of gestation respectively and
served as control groups.
Group(3): Benzo[a]pyrene was given at the dose 12.5 mg/kg at 8th, 12th
and from 8th → 12th day of gestation.
Group(4): The pregnant animals were given B(a)P at dose 50 mg/kg
b.wt. at 8th , 12th and 8th →12th day of gestation .
Group (5): The animals were given B(a)P at dose 100 mg/kg b.wt. at 8th
12th and 8th→12th day of gestation (period of organogenesis). Morphological studies:
Mother’s weights, weight of uteri, percentage of abortion and
resorption were recorded.
Number of implantation sites, number of live and dead fetuses,
average weight and average length of fetuses and external anomalies (as
hematoma) were recorded.
* Skeletal and cartilage:
Skeletal abnormalities were examined using alizarin red stain for
fetal bone and alcian blue for cartilage.
* Histological and Molecular studies:
The liver is the target organ for examined. The livers of pregnant
rats and their fetuses were divided into two parts, the first part of liver
was stored at -20O used for DNA fragmentation test and ,while the second
part of liver was washed in saline and immediately fixed into 10%
formalin for histological examination.
* chromosomal aberration studies:-
In the second experiment the pregnant rats administered B(a)P on
three doses 12.5 , 50 and 100 mg/kg at 8th , 12th and from 8th to the
12th day of gestation. The animals from each group were sacrificed after
24 hours of latter treatment by cervical dislocation. chromosomal
aberrations and molecular alterations to pregnant rats and their fetuses
were studied. The obtained results showed the following:
1. Benzo(a)pyrene in different doses and in different periods of gestation
produced a decrease in weight of placenta and body weight gain of
pregnant rats. Fetal growth retardation represented by the reduction of
fetal body weights and length. Resorption of fetuses and abortion
percentages were significantly increased in high dose 100 mg/kg as
compared to the control group.
2. Skeletal and cartilaginous examinations revealed incomplete
ossifications in bones of skull, pelvic girdles , fore and hind limbs with
missed ossifications of phalanges.
3. Histological examinations in liver of mothers and their fetuses
revealed that dilated and congested central and portal vein and
sinusoids, stromal hemorrhage, inflammation , leucocytic infiltration,
fatty degeneration, necrosis and fibrosis. Multiple numbers of
multinucleated giant cells, especially in fetuses
4. chromosomal aberrations for pregnant rats’ bone marrow and body cells of
their fetuses in a gestation age doses dependent manner. B[a]P induced
significant (P < 0.05) increases in structural and numerical chromosomal
aberrations in bone marrow cells of pregnant females and body cells of their
embryos at all doses compared to the control group. The chromosomal
aberrations induction was dose- and time of gestation age - dependent
manner. The repeated doses (from the 8th to 12th day of gestation) of 12.5,
50 and 100 mg/kg. b. wt. showed the highest significances (P < 0.001) in
averages of chromosomal aberrations than those treated with the single dose
at 8th day and 12th day of gestation in treated pregnant albino rats and its fetuses. Moreover, the percentages of structural chromosomal aberrations
of pregnant maternally were commonly observed than the fetuses but the
numerical chromosomal aberrations of fetuses is highly increased than the
pregnant maternally. In more addition, the fetuses are more sensitivity than
pregnant maternally in percentage of chromosomal aberrations.
5. Molecular apoptosis detection, liver cells of animals treated with
benzo(a)pyrene showed an increase in the intensity of apoptotic bands ,
DNA fragmentation.
Conclusion
In view of the previously mentioned results, the following
could be concluded:
Benzo(a)pyrene has mal-morphogenetic potential that resulted
significant in susceptibility to the growth retardation and malformation
of fetuses maternally treated with the drug.
Severe histological damages in liver of mothers and their fetuses .
Benzo(a)pyrene induced increasing in DNA damage and
chromosomal aberrations in pregnant and their fetuses at all periods of
the time and doses