Differential effects of sulphur mustard on S-phase cells of primary fibroblast cultures from Syrian hamsters.
Sulphur mustard (SM) (5 x 10(-8) M) given to primary Syrian hamster fibroblasts growing short-term in vitro produces a very sharp peak of chromatid aberrations 12-16 h after treatment. The composition of this peak has been investigated in relation to the cell cycle using the facility to divide S-phase into 5 cytologically defined sub-phases on the basis of replication band patterns following bromodeoxyuridine incorporation. It is shown that: (1) Considerable delay and perturbation of the cycle is present. (2) A major contribution to the aberration peak comes from pre-S cells, and the highest aberration frequencies are observed in such cells. (3) The bulk of the contribution from S-cells comes from the last subphase, SkV. (4) The majority of early S cells (sub-phases SkI-IV) fail to reach division within 36 h. Of the total S-cells scored, 54% are non-SkV in controls but only 14% after SM. (5) Aberrations are localized to late-replicating regions in SkV but are random in pre-S. (6) No measurable perturbation of replication programme was found in chromosome arms synthesizing in late SkV after SM. (7) The rapid fall in aberration frequency at later sampling times is consistent with a quick and efficient repair of DNA lesions which is known to occur after SM alkylation. The preferential loss of early S cells seems most likely to result from selective lethality, though differential delay and perturbation may make a contribution. It is interesting to note that the subphases missing are just those where the euchromatin replicates (early replicating R and G bands). The late-replicating chromatin, some of which is known to be dispensable in Syrian hamster, is confined to SkV, the sub-phase which appears to survive this dose of SM.
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects*; D006224:Cricetinae; D007399:Interphase; D008297:Male; D008647:Mesocricetus / Q000235:genetics; D009150:Mustard Compounds / Q000494:pharmacology*; D009151:Mustard Gas / Q000494:pharmacology*; D009153:Mutagens; D012867:Skin / Q000166:cytology / Q000648:ultrastructure
D000477:Alkylating Agents; D009150:Mustard Compounds; D009153:Mutagens; D009151:Mustard Gas