PMID- 3759561
OWN - NLM
STAT- MEDLINE
DCOM- 19861030
LR  - 20190708
IS  - 0360-3016 (Print)
IS  - 0360-3016 (Linking)
VI  - 12
IP  - 8
DP  - 1986 Aug
TI  - Cross-link formation and chemopotentiation of EMT-6/Ro cells exposed to MISO 
      after CCNU treatment in vitro.
PG  - 1389-92
AB  - Experiments were designed to measure cross-link formation following combined 
      treatment of EMT-6/Ro tumor cells with 
      1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and misonidazole (MISO) in 
      vitro. To avoid MISO-induced glutathione (GSH) depletion, which might contribute 
      to enhanced monoadduct formation by reducing the protective GSH pools, a 
      post-incubation (i.e. treatment with CCNU for one hour in air followed by MISO 
      treatment in hypoxia) protocol was adopted. Utilizing this treatment scheme, it 
      was possible to significantly enhance CCNU toxicity by post-treating with MISO 
      immediately after exposure to CCNU. Enhanced cross-link formation detected by 
      alkaline elution, at this time, correlated well with the magnitude of cell-kill 
      enhancement, thereby implicating enhanced cross-link formation in the mechanism 
      of potentiation. However, if the cells were allowed to incubate for various 
      intervals between CCNU and MISO treatments, the magnitude of potentiation 
      progressively diminished. Beyond approximately 8-10 hours (corresponding to the 
      time required for maximal cross-link formation after CCNU treatment), treatment 
      with MISO was ineffective at potentiating CCNU cytotoxicity. These experiments 
      suggest that chemopotentiation can be produced by treating with MISO after 
      treatment with CCNU (post-incubation) and that enhanced cross-link formation is 
      involved in the mechanism of MISO chemopotentiation of CCNU activity. The kinetic 
      studies, using the post-incubation protocol, further suggest that the 
      chemopotentiating effect of MISO is exerted subsequent to monoadduct formation 
      and probably does not involve inhibition of DNA-DNA cross-link repair.
FAU - Mulcahy, R T
AU  - Mulcahy RT
LA  - eng
GR  - CA11198/CA/NCI NIH HHS/United States
GR  - CA32374/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Int J Radiat Oncol Biol Phys
JT  - International journal of radiation oncology, biology, physics
JID - 7603616
RN  - 0 (Antineoplastic Agents)
RN  - 7BRF0Z81KG (Lomustine)
RN  - 8FE7LTN8XE (Misonidazole)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Drug Synergism
MH  - In Vitro Techniques
MH  - Lomustine/*pharmacology
MH  - Misonidazole/*pharmacology
MH  - Neoplasms, Experimental/pathology
EDAT- 1986/08/01 00:00
MHDA- 1986/08/01 00:01
CRDT- 1986/08/01 00:00
PHST- 1986/08/01 00:00 [pubmed]
PHST- 1986/08/01 00:01 [medline]
PHST- 1986/08/01 00:00 [entrez]
AID - 0360-3016(86)90178-1 [pii]
AID - 10.1016/0360-3016(86)90178-1 [doi]
PST - ppublish
SO  - Int J Radiat Oncol Biol Phys. 1986 Aug;12(8):1389-92. doi: 
      10.1016/0360-3016(86)90178-1.