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| Association of intrauterine benzo[a]pyrene exposure with benzo[a]pyrene diolepoxide (BPDE)-DNA adduct levels and pancreatic functional impairment in offspring rats |
| CUI Rong1, ZHENG Yujian2, LU Ying3, Xialidan Alifu2
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1. School of Nursing, Xinjiang Medical University, Urumqi, Xinjiang 830011, China;
2. Xinjiang Medical University, Urumqi, Xinjiang 830011, China;
3. Hainan Medical University, Haikou, Hainan 570216, China |
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Abstract Objective To investigate the benzo[a]pyrene ( B[a]P ) diolepoxide ( BPDE )-DNA adduct levels in offspring rats with intrauterine exposure to B[a]P, and examine the effects of BPDE-DNA adduct levels on pancreatic functional impairment and glucose metabolism in offspring rats. Methods Forty pregnant rats were randomly divided into the blank control group, standard-dose group, low-dose group, medium-dose group and high-dose group (daily dose of 0, 2, 200, 800, 1 600 μg/kg B[a]P, respectively), of 8 animals in each group. Rats in the B[a]P treatment groups were administered by oral gavage with a mixture of B[a]P and corn oil at a dose of 0.2 mL/100 g body weight since day 1 of pregnancy until 21 days after delivery, while rats in the blank control group were given the same volume of coin oil by oral gavage. The BPDE-DNA adduct levels were measured and the pancreatic development was observed in the offspring rats 2 and 21 days and 12 weeks after birth, and the correlation between pancreas volume index and dose of exposure to B[a]P was examined using Spearman's rank correlation analysis. In addition, glucose metabolism was measured in offspring rats 12 months after birth using glucose tolerance test ( GTT ) and insulin tolerance test ( ITT ). Results There was no abnormal appearance, death, abortion or preterm birth in pregnant or offspring rats in the five groups, and no significant differences were seen in activity, diet, drinking water or mental status in rats. The greatest level of BPDE-DNA adducts was measured in offspring rats 2 days after birth, with median levels ( interquartile range ) of 1 089.60 ( 586.10 ) to 1 405.49 ( 346.47 ) pg/mL, and no BPDE-DNA adducts were found in offspring rats 12 weeks after birth. The pancreas volume index correlated negatively with the dose of exposure to B[a]P in offspring rats 2 ( rs=-0.620, P=0.001 ) and 21 days after birth ( rs=-0.801, P=0.001 ). Hypoplasia of pancreas with loose tissues was seen in offspring rats 2 days after birth, while well pancreatic development was found in offspring rats 12 weeks after birth, with tight exocrine portion. GTT showed an increase in glucose levels in offspring rats in all five groups following abdominal injection of glucose and declined 30 min post-injection ( F=365.578, P<0.001 ), and ITT showed a tendency towards a decline in glucose levels in offspring rats in all five groups ( F=461.215, P<0.001 ). Conclusions The levels of BPDE-DNA adducts in offspring rats increase with the dose of intrauterine B[a]P exposure, and insulin resistance and impaired glucose tolerance occur 12 months post-exposure to B[a]P. Intrauterine B[a]P exposure affects pancreatic development in offspring rats and causes abnormal glucose metabolism in adult offspring rats.
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Received: 27 September 2021
Revised: 02 February 2022
Published: 13 April 2022
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