Bleomycin-induced chromosome damage in lymphocytes indicates inefficient DNA repair capacity in breast cancer families.
In vitro mutagen susceptibility has been observed as a predictor of cancer risk. To evaluate susceptibility to mutagen, we have studied the response to in vitro bleomycin (BLM) treatment in cultured peripheral blood lymphocytes (PBL) of 9 breast cancer families (BCFs). Eleven breast cancer patients (BCPs) and 36 healthy blood relatives (HBRs) from BCFs were included in the study. Data were compared with 22 healthy control women. The frequencies of chromosomal aberrations were evaluated after exposure to BLM in the last five hours. Mean frequency of BLM-induced chromosomal aberrations per cell (CA) observed among BCPs was significantly higher as compared to their HBRs as well as control subjects. Moreover, mean BLM-induced CA/cell value observed for HBRs was also significantly higher than that of control subjects. In comparison to controls, it was observed that there was four times more cancer risk in BCPs (OR=4.148, 95% CI=5.83-687.46) and 2.5 times more cancer risk in HBRs (OR=2.67, 95% CI=5.31-39.25). Lymphocytes from 90% of BCPs and 69% of HBRs were found to be sensitive to BLM (using a cutoff value = controls group mean + 1 SD). Thus, lymphocytes of BCPs and their HBRs were more sensitive to BLM exposure as compared to controls. Our finding indicated inefficient DNA repair capacity in BCFs. The HBRs in BCFs, having increased BLM-sensitivity, may be at higher risk to develop a similar cancer.
Roy
S K
SK
Cell Biology Division, The Gujarat Cancer Society, Asarwa, Ahmedabad, India.
Trivedi
A H
AH
Bakshi
S R
SR
Patel
S J
SJ
Shukla
P H
PH
Bhatavdekar
J M
JM
Patel
D D
DD
Shah
P M
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D002842:Chromatids / Q000187:drug effects / Q000378:metabolism; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002877:Chromosomes, Human / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008677:Metaphase / Q000235:genetics; D008875:Middle Aged; D012680:Sensitivity and Specificity
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D001761:Bleomycin