32P-postlabelled DNA adducts in liver obtained from women treated with tamoxifen.
32P-Postlabelling of DNA extracted from the livers obtained from seven women receiving tamoxifen (20 mg either once or twice daily) was compared with liver DNA from seven individuals not receiving this drug. In all but one of the treated women, tamoxifen and its N-desmethyltamoxifen metabolite could be detected in liver extracts by high performance liquid chromatography; none was detected in control samples. The total level of 32P-postlabelled DNA adducts extracted from the tamoxifen treated women ranged between 18-80 adducts/10(8) nucleotides. The pattern of 32P-postlabelled adducts was not the same as those seen in rats dosed with this drug. There was no significant difference in the level of DNA damage between the tamoxifen treated and control groups. Although only a small number of subjects has so far been examined it appears that women are less susceptible to liver DNA damage caused by tamoxifen than rats.
Martin
E A
EA
MRC Toxicology Unit, University of Leicester, UK.
Rich
K J
KJ
White
I N
IN
Woods
K L
KL
Powles
T J
TJ
Smith
L L
LL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001345:Autoradiography; D004247:DNA / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism*; D018736:DNA Adducts / Q000032:analysis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D008875:Middle Aged; D010761:Phosphorus Radioisotopes; D013629:Tamoxifen / Q000009:adverse effects* / Q000378:metabolism*; D013997:Time Factors
D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D013629:Tamoxifen; D004247:DNA