Comparison of cell‐cycle phase perturbations induced by the DNA‐minor‐groove alkylator tallimustine and by melphalan in the SW626 cell line

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Abstract
Tallimustine or N‐deformyl‐N‐[4‐N‐N,N‐bis(2‐chloroethylamino)benzoyl], a distamycin‐A derivative (FCE 24517), is a novel anti‐cancer agent which alkylates N3 adenine in the minor groove of DNA. The cell‐cycle phase perturbations induced by the drug were investigated and compared with those caused by melphalan (L‐PAM) in SW626 human ovarian‐cancer cells. By coupling bromodeoxyuridine (BUdR) immunoreaction with biparametric flow‐cytometric (FCM) analysis, we investigated the cell‐cycle phase perturbation induced by tallimustine or L‐PAM, considering separately the cells which, during the 1‐hr treatment, were in the S phase or in G1‐G2/M phases of the cell cycle. L‐PAM delayed the S‐phase progression of cells exposed to the drug when they were in S phase, with a consequent accumulation of cells as soon as they reached the G2 phase. In contrast, the S‐phase cells treated with tallimustine were not perturbed during the DNA‐synthesis phase progression, and were blocked in G2 only after they had passed through the G1/S transition of a new cell cycle. In cells which were in G1 or G2/M phases during drug treatment, tallimustine and L‐PAM caused similar accumulation in G2. The differences in the cell‐cycle perturbation caused by tallimustine and L‐PAM may well be related to the different DNA damage the 2 drugs produced. These findings emphasize the different properties of DNA‐minor‐groove alkylating agents and conventional ones.

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