Enhanced sensitivity of peripheral blood lymphocytes from women carrying a BRCA1 mutation towards the mutagenic effects of various cytostatics.

摘要: Abstract We are studying the induction and repair of DNA damage in lymphocytes women from families with familial breast cancer mutations susceptibility genes BRCA1 BRCA2 . Our previous results indicated a close relationship between presence mutation sensitivity for micronuclei by gamma irradiation hydrogen peroxide (H 2 O ). To further characterize mutagen to better understand underlying mechanisms, we now tested effect various cytostatics on micronucleus frequencies comparison controls. The presented here indicate enhanced towards bleomycin, cisplatin, cyclophosphamide bischloroethylnitosurea (BCNU). However, cisplatin BCNU was not accompanied sister chromatid exchanges (SCE), suggesting that intrachromosomal recombination is affected. In contrast DNA-damaging agents, there no clear difference response vincristine taxol. FISH analysis revealed two aneugens mainly induced centromere-positve similar extent without mutation. conclude cells containing heterozygous more sensitive different kinds accordance proposed central role maintaining genomic integrity. Although has been shown interact mitotic spindle, spindle poisons do cause micronuclei. Since some mutagens used as chemotherapy, it might be at higher risk secondary cancers standard therapies.