Abstract：
:Daily oral administration of either 20, 40 or 60 mg/kg chlorphentermine for 7 days significantly increased liver and kidney DNA levels, which were not elevated further even after a 3 week treatment period. Although cessation of drug administration for 3 weeks resulted in a return of hepatic DNA levels to control values, a rise in renal DNA was still observed after this withdrawal period. Whereas 20 mg/kg chlorphentermine for 7 days failed to markedly alter the incorporation of thymidine into kidney and liver DNA, significant enhancement was noted in neonates receiving 40 or 60 mg/kg drug and quantitatively greater incorporation occurred when the agent was given for 21 days. While a signficant augmentation in nucleic acids synthesis was seen 1 week after animals were removed from 40 or 60 mg/kg anorectic, a restoration to control levels occurred after a 3 week abstinence period. Treatment with 20 mg/kg for 1 week followed by withdrawal resulted in a significant rise in the incorporation of thymidine into renal and hepatic DNA. In contrast, drug administration for 3 weeks followed by 21 days abstinence resulted in a return to control levels in the incorporation of thymidine into kidney and liver DNA, except for renal tissue removed from 20 mg/kg. Our data demonstrate that the chlorphentermine-induced alterations in renal and hepatic DNA metabolism are dose-dependent, related to duration of exposure as well as reversible.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Kacew S,Dubas TC,Stevenson AJdoi
10.1016/0300-483x(78)90057-4subject
Has Abstractpub_date
1978-05-01 00:00:00pages
77-90issue
1eissn
0300-483Xissn
1879-3185journal_volume
10pub_type
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