Temporal SCE and cytotoxicity responses of murine cells following in vivo treatment with MNU or L-PAM.
Time-dependent SCE responses of bone marrow and cultured spleen lymphocytes of BDF1 mice to in vivo treatment with MNU or L-PAM were studied. L-PAM was generally more active than MNU in producing elevated SCEs. Increases of 4-5 times control levels were produced in lymphocytes cultured at 1 or 24 h after i.p. injection of 4.95 mumoles/kg of L-PAM whereas an approximately 3-fold increase was produced by an acute injection of 190 mumoles/kg of MNU. Temporal SCE responses of bone marrow cells were carried out with doses of L-PAM (4.95 mumoles/kg) and MNU (131 mumoles/kg) found to be noncytotoxic by analysis of relative percentages of first, second, and third generation cells. The SCE response of second generation bone marrow cells (greater than 7 time baseline) to MNU was maximum when treatment was at the first cycle and decreased rapidly with increasing time prior to, or after the start of BrdUrd infusion. By contrast nonreciprocal (NR) SCE responses of third generation progeny never exceeded a 2-fold increase over baseline. Dramatic inhibition of cell cycling by MNU was evident as the reciprocal (R) SCEs in third generation cells increased, and exceeded NR SCEs, with increased treatment time intervals after the start of BrdUrd infusion. Similar dramatic cytotoxicity of L-PAM was apparent in time-dependent SCE response studies. An increased BrdUrd infusion time (28 h rather than the usual 26.5 h) was necessary to achieve adequate numbers of third division cells. Maximum SCE responses of the latter cells to L-PAM did not exceed 3 times baseline levels, whereas maximum responses of greater than 9 times control levels were produced in second generation cells. Comparison of SCE responses of second and third generation progeny of similarly treated cell populations, appears to provide a more sensitive assessment of cytotoxicity than does the conventional method of cell cycle analysis.
Conner
M K
MK
Departments of Biostatistics, Graduate School of Public Health, University of Pittsburgh, PA 15162.
Guzzie
P J
PJ
Neft
R E
RE
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008558:Melphalan / Q000633:toxicity*; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D009153:Mutagens; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013997:Time Factors
D009153:Mutagens; D008770:Methylnitrosourea; D008558:Melphalan