Breast Cancer Risk Factors Among Screening Program Participants

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Abstract
Cells from a line (SN1029) derived from a case of chronic lymphocytic leukemia (CLL) were highly sensitive to the killing effects of chemical agents [4-nitroquinoline 1-oxide (4NQO), methyl methanesulfonate, ethyl methanesulfonate (EMS), mitomycin C (MMC), daunomycin (DM), bleomycin, and cytosine arabinoside], as compared to the lack of sensitivity of a normal lymphocytic cell line treated with these agents. Cells treated with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) were a possible exception to this pattern. Among the chemicals tested, SN1029 cells were extremely sensitive to MMC with regard to frequency of sister chromatid exchange(s) (SCE), even though MMC did not greatly increase the incidence of chromosome aberrations. Reverse results were obtained with the 6 other chemicals, i.e., no significant increase in SCE but a definite rise in chromosome aberrations. However, some contrasting results were obtained; e.g., DM induced a high frequency of chromosome aberrations in normal and SN1029 cells without a concomitant increase in SCE frequency. Unscheduled DNA synthesis (USD) in normal and SN1029 cells was examined following UV radiation (200 ergs/ mm2) and chemical treatments with EMS, MNNG, MMC, and 4NQO for 90 minutes at 6.0 µg/ml (expt I) and for 48 hours at 0.003, 0.03, 0.3, and 6.0 µg/ml (expt II). Almost no detectable levels of USD were seen with MMC in experiment I or with MMC, EMS, MNNG, and 4-NQO in experiment II, whereas USD did occur following 4-NQO, EMS, MNNG, and UV radiation in experiment I. The repair level did not differ between normal and SN1029 cells when exposed to EMS, MNNG, 4-NQO, and UV radiation, in spite of hypersensitivity of the SN1029 cells to the killing effects of 4-NQO and EMS. Comparison of SCE breakpoints and USD (shown by the g rain distribution) indicated that the SCE breakpoints within chromosome #1 in MMC- and 4-NQO-treated normal cells were nonrandom, whereas the silver grains were distributed randomly over the chromatids in cells treated with 4-NQO. The results indicate that SCE and excision repair are not closely linked and that the high SCE sensitivity and cell death of the CLL cell line are independent of the quantitative capacity of excision repair.