1Alpha,25-dihydroxyvitamin D3 inhibits hepatic chromosomal aberrations, DNA strand breaks and specific DNA adducts during rat hepatocarcinogenesis |
| |
Authors: | Saha B K Bishayee A Kanjilal N B Chatterjee M |
| |
Institution: | (1) Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Calcutta 700 032 (India), Fax +33 473 4665, e-mail: m_chatterjee@lycos.com , IN;(2) Present address: Division of Radiation Research, MSB F-451, Department of Radiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark (New Jersey 07103, USA), US |
| |
Abstract: | The possible promoting effect of streptozotocin (STZ; 65 mg/kg body weight, intraperitoneal)-induced diabetes during 2-acetylaminofluorene
(2-AAF; 0.04% in basal diet)-initiated hepatocarcinogenesis and modulatory effect of 1α,25-dihydroxyvitamin D3 (VD3; 0.3 μg/0.1 ml in propylene glycol, per os) were investigated by monitoring chromosomal aberrations (CAs), DNA strand breaks
and specific DNA adducts in rat liver. VD3 treatment (twice a week) was started 4 weeks before the 2-AAF regimen and continued throughout the study. Aberrant metaphase
chromosomes were counted from the regenerating hepatocytes 15, 30 or 45 weeks after STZ injection, while DNA strand break
and adduct assays were performed 45 days post-STZ treatment. Dietary exposure to 2-AAF elicited a substantial increase in
CAs and elevated the extent of DNA strand breaks and formation of N-(deoxyguanosin-8-yl)-2-aminofluorene. A promoting effect of STZ was evident from CAs coupled with DNA strand break analysis.
VD3 treatment substantially reducted 2-AAF+STZ-induced CAs as well as DNA strand breaks and adducts. Thus, VD3 appears to be effective in suppressing liver-specific early chromosomal as well as DNA damage during the process of rat hepatocarcinogenesis
initiated with 2-AAF and promoted by STZ contributing to its promise as a cancer chemotherapeutic agent.
Received 27 April 2001; accepted 22 May 2001 |
| |
Keywords: | : 2-Acetylaminofluorene streptozotocin vitamin D3 chromosomal aberration DNA strand break DNA adduct rat liver |
本文献已被 PubMed SpringerLink 等数据库收录! |
|