Potentially lethal damage repair by total and quiescent tumor cells following various DNA-damaging treatments.
After continuous labeling of proliferating (P) cells with 5-bromo-2'-deoxyuridine (BrdU) for 5 days, SCC VII tumor-bearing mice received various kinds of DNA-damaging treatments: gamma-ray irradiation, tirapazamine (TPZ, hypoxia-specific cytotoxin) administration, or cisplatin injection. From 0.5 to 72 hr after treatment, tumors were excised, minced, and trypsinized. Single tumor cell suspensions were incubated for 48 hr with a cytokinesis-blocker, cytochalasin-B. Then, the micronucleus (MN) frequency for BrdU-unlabeled cells, quiescent (Q) cells at treatment, was determined using immunofluorescence staining for BrdU. The MN frequency for total (P+Q) cells was obtained from tumors that were not pretreated with BrdU labeling. The sensitivity to each DNA-damaging treatment was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency). Treatment with gamma-rays or cisplatin resulted in a larger MN frequency in total cells than in Q cells. In contrast, TPZ treatment produced a smaller MN frequency in total cells than in Q cells. Regardless of the treatment used, Q cells showed greater repair capacities than total cells. However, TPZ caused much smaller repair capacity in both total and Q cells, compared with gamma-rays or cisplatin. Gamma-rays and cisplatin produced similar repair patterns. Differences in sensitivity between total and Q cells and repair patterns of the two cell populations were thought to depend on differences between the two cell populations in the toxicity of the DNA-damaging treatment and distribution pattern of the anticancer agent.
Masunaga
S
S
Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University, Japan.
Ono
K
K
Hori
H
H
Suzuki
M
M
Kinashi
Y
Y
Takagaki
M
M
Kasai
S
S
Nagasawa
H
H
Uto
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000627:therapeutic use; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair; D004273:DNA, Neoplasm; D005260:Female; D005455:Fluorescent Antibody Technique; D005720:Gamma Rays / Q000627:therapeutic use*; D007928:Lethal Dose 50; D051379:Mice; D008809:Mice, Inbred C3H; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D018714:Radiotherapy, Adjuvant; D000077704:Tirapazamine; D014227:Triazines / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin