Absence of DNA adduct in the leukocytes from breast cancer patients treated with toremifene.
Tamoxifen (TAM) causes cancer in rat liver and human endometrium, whereas the carcinogenicity of its chlorinated analogue toremifene (TOR) has not been observed. To elucidate the genotoxicity of TOR, the capability of forming DNA adducts by TOR was examined in the leukocytes of patients treated with TOR. Leukocytes were collected from 27 breast cancer patients (57.7 +/- 11.4 years old) taking TOR (40 mg/day for 25 patients, 80 mg/day for one patient, and 120 mg/day for one patient; average duration, approximately 12 months) and 20 untreated breast cancer patients (58.2 +/- 12.3 years old). The DNA extracted was analyzed by (32)P-postlabeling/high-performance liquid chromatography. No DNA adducts were detected in the leukocytes of either TOR-treated or nontreated patients. Our results contrast to the previous observation detecting TAM-DNA adducts in several patients treated with TAM, indicating that TOR is less genotoxic to humans.
Umemoto
Atsushi
A
Department of Oncological and Regenerative Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan. aummt@clin.med.tokushima-u.ac.jp
Lin
Chun-Xing
CX
Ueyama
Yuji
Y
Komaki
Kansei
K
Santosh Laxmi
Y R
YR
Shibutani
Shinya
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use / Q000633:toxicity*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000032:analysis*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000187:drug effects / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000737:chemistry*; D008875:Middle Aged; D017312:Toremifene / Q000627:therapeutic use / Q000633:toxicity*
D018931:Antineoplastic Agents, Hormonal; D018736:DNA Adducts; D004273:DNA, Neoplasm; D017312:Toremifene