PMID- 7895867
OWN - NLM
STAT- MEDLINE
DCOM- 19950424
LR  - 20190909
IS  - 0029-0661 (Print)
IS  - 0029-0661 (Linking)
VI  - 71
IP  - 1
DP  - 1995 Jan 20
TI  - [Different effects of anticancer drugs on two human thyroid cell lines with 
      different stages of differentiation].
PG  - 73-86
AB  - We established two human thyroid tumor cell lines. One cell line (hPTC) was 
      established from the tissue of a papillary thyroid carcinoma surgically excised 
      from a 27-year-old female patient. The other cell line (hAG) was established from 
      the tissue of an adenomatous goiter excised from a 59-year old female patient. 
      Synthesis of cAMP by hPTC and hAG increased when they were stimulated by TSH. 
      hPTC and hAG continued to divide as a monolayer in a tissue culture for three 
      years and two years, respectively. We assessed the efficacy of anticancer drugs 
      (doxorubicin:ADR, cisplatin:CDDP, nimustine:ACNU, bleomycin:BLM, 
      cyclophosphamide:CPA, aclarubicin:ACR) with resard to hPTC. The hPTC cells were 
      cultured in 24-well plates in the presence of the anticancer drugs for 48 hours, 
      and the cellular DNA of the live cells was measured with diaminobenzoic acid. ADR 
      had the lowest ED50 (0.029 mu g/ml) and the clinical blood concentration was 13.8 
      times that of the ED50. The clinical blood concentration divided by ED50 for the 
      other anticancer drugs are, in order of higher values, 2.3 for CPA, 1.7 for BLM, 
      1.2 for CDDP, 0.5 for ACR, and less than 0.1 for ACNU. ADR showed 
      time-independent effects since a 2-hour exposure of ADR to the hPTC cells 
      resulted in the significant reduction of the cellular DNA content of the live 
      cells even after 48 hours. The effects of the other anticancer drugs were 
      time-dependent. We then studied the difference of the effects of ADR on hPTC and 
      hAG. ED50 for hPTC was significantly low (0.035 mu g/ml) compared to that for hAG 
      (0.460 mu g/ml). Since free radical formation is one of the major anticancer 
      mechanisms of ADR the effects of free radicals on ED50's for hPTC and hAG were 
      measured by adding glutathione (GSH), N-acetylcystein (NAC), buthionine 
      sulfoximine (BSO), and alpha-tocopherol (alpha-toco) into the culture media. GSH 
      catches up with free radicals in the extracellular fluid. NAC promotes production 
      of GSH in the cytoplasm, but BSO interferes with the production of GSH in the 
      cytoplasm. alpha-toco catches up with free radicals on the plasma membrane. GSH 
      and alpha-toco did not effect ED50 for hPTC and hAG. However, NAC increased ED50 
      for hPTC and hAG, and BSO reduced ED50 for hPTC and hAG. The effects of NAC and 
      BSO on ED50 for hPTC were greater than those for hAG.(ABSTRACT TRUNCATED AT 400 
      WORDS)
FAU - Yamanaka, T
AU  - Yamanaka T
AD  - Department of Endocrinology, Dokkyo University School of Medicine, Tochigi, 
      Japan.
FAU - Hishinuma, A
AU  - Hishinuma A
LA  - jpn
PT  - Case Reports
PT  - Comparative Study
PT  - English Abstract
PT  - Journal Article
PL  - Japan
TA  - Nihon Naibunpi Gakkai Zasshi
JT  - Nihon Naibunpi Gakkai zasshi
JID - 0413717
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Free Radicals)
SB  - IM
MH  - Adenoma/*pathology
MH  - Adult
MH  - Antineoplastic Agents/*pharmacology
MH  - Carcinoma, Papillary/*pathology
MH  - Cell Division/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Free Radicals/metabolism
MH  - Humans
MH  - Middle Aged
MH  - Thyroid Neoplasms/*pathology
MH  - Time Factors
MH  - Tumor Cells, Cultured/drug effects
EDAT- 1995/01/20 00:00
MHDA- 1995/01/20 00:01
CRDT- 1995/01/20 00:00
PHST- 1995/01/20 00:00 [pubmed]
PHST- 1995/01/20 00:01 [medline]
PHST- 1995/01/20 00:00 [entrez]
AID - 10.1507/endocrine1927.71.1_73 [doi]
PST - ppublish
SO  - Nihon Naibunpi Gakkai Zasshi. 1995 Jan 20;71(1):73-86. doi: 
      10.1507/endocrine1927.71.1_73.