Linked Life Data

7565897

Source:http://linkedlifedata.com/resource/pubmed/id/7565897

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1995-10-25
pubmed:abstractText
Tacrine (1,2,3,4-tetrahydro-9-aminoacridine; THA), a reversible centrally acting anticholinesterase, has been shown to be potentially useful for treatment of patients with Alzheimer's disease. However, currently available forms of THA may be therapeutically limited by the fact that high doses have resulted in liver and kidney damage. To determine if THA is hepatotoxic via a genotoxic mechanism, we evaluated its ability to induce unscheduled DNA synthesis (UDS) in primary cultures of rodent hepatocytes. Positive dose-dependent increases in UDS were observed in hepatocytes derived from male B6C3F1 mice and from young, middle-aged, old, and old Aroclor-induced (ARO) male F344 rats maintained on either an ad libitum (AL) or a caloric restricted (CR) diet (60% of AL) and exposed to 0.05-1000.0 micrograms/ml of THA. Hepatocytes from old AL rats, treated with THA, exhibited significant age-related decreases in DNA repair compared to young and middle-aged AL rats. By contrast, cultures from CR rats exhibited age- and diet-related decreases in UDS from the AL and young CR animals, respectively. Moreover, ARO-induced old AL- and CR-derived hepatocytes exhibited significant increases in UDS compared to uninduced old AL and CR animals. No cytotoxicity was observed in the uninduced old AL- or any CR-derived hepatocytes. These data indicate that the aged and CR fed animal is less susceptible to the cytotoxic and genotoxic effects of THA; while the younger AL fed and enzyme induced old AL or CR fed animals were more susceptible. The data suggest that THA may be a genotoxic rodent carcinogen. At present, the relationship of these findings to the clinical use of THA are unclear and further study is required.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:volume
344
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
79-88
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Genotoxicity of tacrine in primary hepatocytes isolated from B6C3F1 mice and aged ad libitum and calorie restricted Fischer 344 rats.
pubmed:affiliation
Division of Genetic Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA.
pubmed:publicationType
Journal Article