Determination of the target volume of hela cells treated with tetra‐ and hexa‐ chloroplatinates

Abstract

HeLa S‐3 cells were treated with ^l95mPt‐radiolabeled tetra‐ and hexa‐chloroplatinums (Pt(II) and Pt(IV)) under various conditions, and the relationship between lethal effect and the number of Pt‐atoms binding to DNA, RNA and proteins was examined. The mean lethal concentrations for the cells treated with Pt(II) at 37°C for 1, 2 and 3 h were 163.5, 126.2 and 67.3 μM, while those for Pt(IV) were 78.6, 53.4 and 35.9, respectively. By using identically treated cells, the number of Pt‐atoms combined with DNA, RNA and protein molecules were determined after the cell were fractionated using the method of Schneider [ref. 1]. In this way, the D_o values given as the drug concentration were substituted for the number of Pt‐atoms combined with each fraction, then, the target volumes expressed as the reciprocals of D_o values were calculated for each fraction. The results suggested that DNA and high molecular weight RNAs (except t‐RNA), under some limited condition, can be the target molecules for cell killing by both the compounds. The target volumes for DNA were 3.15x10³ 3.75x10³ and 5.86x10³ nucleotides for 1.2 and 3 h Pt(II)‐treated cells, while those for Pt(IV) were 4.27X10³, 4.58X10³ and 6.37xl0³ nucleotides, respectively. This means that no significant difference between the two platinates can be detected on the efficiency for Pt‐atom to kill the cell. Cell killing effects of Pt(IV) was lower than CDDP (see ref. 7) by a factor of 12–16 according to the treatment, but higher than TDDP (see ref. 8) by a factor of 1.4–2.5.

Key words:

• Platinum(II)chloride
• platinum(IV)chloride
• cisplatin
• HeLa cell
• cell killing
• target volume