Caffeine, caffeine derivatives and chromosomal aberrations. III. The ATP-dependence of the production of chromosomal aberrations by 8-ethoxycaffeine in Chinese hamster cells at 17 degrees C.

Abstract

The effects of caffeine, 8-ethoxycaffeine(EOC), and 6-methylcoumarin (6-MC) on chromosome structure were studied with root tips of Allium proliferum (Egyptian or tree onion) and cell cultures of the Chinese hamster as experimental materials. The results indicate that the three substances produce chromosomal aberrations by similar mechanisms. Root tips were treated at 20°C. The majority of the aberrations were obtained in cells exposed during late G2 and prophase, and “subchromatid” and chromatid exchanges predominated among the aberrations produced. The effect was dependent on the ATP concentration in the roots. Very few aberrations were produced when the generation of ATP was suppressed by anoxia or by sodium azide. On a molar basis, EOC was approximately four times more active than caffeine. When treated at 37°C, Chinese hamster cells were affected during the interphase period of DNA synthesis (the S-phase). The effect consisted of a pronounced fragmentation of chromatids. The aberrations were produced independently of the concentration of ATP in the cells. At 37°C, caffeine and EOC were about equally effective as chromosome-breaking agents. When treated at 17°C, Chinese hamster cells responded to caffeine and EOC in very much the same way as did plant cells. The majority of the aberrations were produced in cells treated during prophase or G2. About half of these aberrations (gaps excluded) were “subchromatid” and chromatid exchanges. However, the frequencies of chromatid breaks and the degree of incompleteness of the exchanges were considerably higher in hamster cells than in Allium root tips. EOC was considerably more effective than caffeine. The effect was dependent on ATP.