Study to elucidate molecular mechanism behind zinc chemo-preventive role during lung carcinogenesis.
The present planned to elucidate the mechanistic role zinc supplementation in the modulation of p53 post-translational acetylation, the activity of cyclooxygenase-2 (COX-2) along with other biophysical parameters during benzo(a)pyrene (BP) induced lung carcinogenesis in mice.



The mice were segregated into four groups viz., normal control, BP treated, BP + zinc and zinc alone treated. Lung carcinogenesis was induced by a single intra-peritoneal (IP) injection of BP (100 mg/kg body weight). Zinc was supplemented to mice at dose levels of 227 mg/kg body weight in drinking water. All the treatments were continued for 20 weeks.



The BP caused a significant rise in the expression of p53. On the other hand, protein expressions of acetylated (lys382)-p53 were significantly decreased, following BP treatment. Also, a significant decrease was observed in the enzyme activities of caspase 3 and caspase 9. Moreover, BP treatment brought about a significant increase in the activity of COX-2. Supplementation of zinc to BP treated mice stimulated acetylation of p53 as observed by an increase in the protein expression of acetylated (lys382)-p53. Also, the enzyme activities of caspase 3 and caspase 9 showed a significant elevation upon zinc supplementation. On the other hand, the zinc supplementation brought about moderation in the expression of enzymatic activity of COX-2 which was restored within the normal limits. Further, BP treatment recorded increased 3H-thymidine uptake as well as enhanced 14C-glucose uptake and its turnover which were reduced significantly following simultaneous treatment with zinc.



The treatment with zinc has the potential to modulate p53 acetylation to stimulate apoptosis against experimentally induced lung carcinogenesis.
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Su Zhou, China. zhenyachen0011@gmail.com.
S-Y
SY
Zhu
J-D
JD
Wang
Y-J
YJ
Lu
Z-Y
ZY
Shen
D000818:Animals; D001564:Benzo(a)pyrene; D063646:Carcinogenesis / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D015032:Zinc / Q000378:metabolism*
D001564:Benzo(a)pyrene; D015032:Zinc