ヒト脳腫瘍由来細胞株における抗癌剤誘発姉妹染色分体交換—殺細胞効果との関連性について

ANTICANCER DRUG INDUCED SISTER CHROMATID EXCHANGE AND CORRELATION TO CELL SURVIVAL IN HUMAN BRAIN TUMOR CELLS

　抄録　ヒト悪性グリオーマより樹立されたSF−126,SF−268,SF−210,SF−295,SF−188の5種類のヒト脳腫瘍細胞株における，1-（4-amino−2-methyl−5-pyrimidinyl） methyl−3-（2-chloroetyl）−3-nitrosoureahydrochloride （ACNU），1,3-bis （2-chloroehyl）−1-nitrosourea （BCNU），nitrogen mustard （HN₂），cis-diamminedichloroplatinum （II）（cis-Pt）の各抗癌剤による姉妹染色分体交換（SCE）誘発を検出し，コロニー形成能試験により測定した殺細胞効果との関連について検索した。各薬剤において1logkillをもたらす薬剤濃度（D₁₀）と誘発されたSCE数を比較すると，ACNUにおけるD₁₀はSF−188＞SF−295＞SF—210＞SF−268＞SF−126であり，SCE誘発はSF−126＞SF−268＞SF−210＞SF−295＞SF−188の順で多くみられ，殺細胞効果が多いほどSCEが高頻度に誘発された。BCNUにおける結果はACNUと同様であったが，HN₂，cis-Ptにおいては，各細胞はニトロソウレア系薬剤と異なる薬剤感受性をしめした。しかしSCE誘発はいずれの薬剤においても殺細胞効果とよく一致した。以上の結果より，広義のアルキル化剤によるSCE誘発は，ヒト悪性脳腫瘍細胞における鋭敏な薬剤感受性試験として使用可能であることが示唆される。

Sister chromatid exchanges (SCEs) induced by four anticancer drugs, 3-(4-amino-2-methyl-5- pyrimidyl) methyl-1-(2-chloroethyl)-1-nitrosourea (ACNU), 1-3-bis (2-chloroethyl)-1-nitrosourea (BCNU), nitrogen mustard (HN₂), cis-diamminedi-chloroplatinum (II) (cis-Pt) were examined on five cell lines derived from human malignant glioma biopsy specimens, and compared to results obtained with colony-forming efficiency (CFE) assay.

Treatment of the five cell lines with these four drugs produced concentration-dependent increa-ses in SCEs. Treatment with ACNU induced the most SCEs in SF-126 cells decreasing in SF-268 cells followed by SF-210 cells, SF-295 cells, and the least SCEs in SF-188 cells. The results of theSCE assay with BCNU in these cell lines were similar with ones with ACNU. In contrast to results obtained with nitrosoureas, the most SCEs were induced in SF-188 cells and the least were induced in SF-126 cells by the treatment of HN₂. The frequency of SCEs induced with cis-Pt was almost similar in the five cell lines.

The number of SCEs induced by the treatment of ACNU, BCNU, HN₂ and cis-Pt in five cells lines showed a good correlation with cytotoxicity measured by CFE assays, and induction of SCEs occured at much lower concentrations of these anticancer drugs than those required to induced cell kill.

These results suggest that measurement of in-duced SCEs in human brain tumor cells treated with some anticancer drugs provide a more sensi-tive indicator of drug action than CFE assay and that SCE assays may be a useful method of the in vitro sensitivity test to some anticancer drugs.