Toxicity of nucleic acid bases on Drosophila cell cultures.

Abstract

Monolayer cultures of Kc-H Drosophila cells were used to detect the effects of purine and pyrimidine compounds. Analysis of the end product of normal metabolism, uric acid, was done to detect effects of exogenous purine and pyrimidine derivatives. It was found that adenine, hypoxanthine, xanthine, and purine were toxic to Kc-H Drosophila cell cultures. A hyperproduction of uric acid was found as a result of adenine, hypoxanthine, and xanthine treatments which was reduced by thymine in both hypoxanthine and xanthine treated cells. These findings conclude that toxicity appears to be due both to an uric acid contribution from purine catabolism plus the ability of the compounds to feedback and starve cells of pyrimidines. This conclusion also was supported by the protective effects seen with guanine, cytosine, and thymidine treatments on adenine-treated cells. The hypothesis states that a possible regulatory connection exists between purine and pyrimidine synthesis probably due to the link of these pathways by their common substrate, phosphoribosylpyrophosphate (PP-ribose-P). Allopurinol, 8-azaguanine, aminopterin, and 2,6 diaminopurine were also tested for effects on Kc-H Drosophila cells. The results showed 2,6 diaminopurine, allopurinol, and aminopterin, by themselves, exerting no toxic effect on Drosophila cells. Allopurinol was found to inhibit hypoxanthine and xanthine toxic effects. Cells toxicity to 8-azaguanine Monolayer cultures of Kc-H Drosophila cells were used to detect the effects of purine and pyrimidine compounds. Analysis of the end product of normal metabolism, uric acid, was done to detect effects of exogenous purine and pyrimidine derivatives. It was found that adenine, hypoxanthine, xanthine, and purine were toxic to Kc-H Drosophila cell cultures. A hyperproduction of uric acid was found as a result of adenine, hypoxanthine, and xanthine treatments which was reduced by thymine in both hypoxanthine and xanthine treated cells. These findings conclude that toxicity appears to be due both to an uric acid contribution from purine catabolism plus the ability of the compounds to feedback and starve cells of pyrimidines. This conclusion also was supported by the protective effects seen with guanine, cytosine, and thymidine treatments on adenine-treated cells. The hypothesis states that a possible regulatory connection exists between purine and pyrimidine synthesis probably due to the link of these pathways by their common substrate, phosphoribosylpyrophosphate (PP-ribose-P). Allopurinol, 8-azaguanine, aminopterin, and 2,6 diaminopurine were also tested for effects on Kc-H Drosophila cells. The results showed 2,6 diaminopurine, allopurinol, and aminopterin, by themselves, exerting no toxic effect on Drosophila cells. Allopurinol was found to inhibit hypoxanthine and xanthine toxic effects. Cells toxicity to 8-azaguanine is probably due to the inhibition of xanthine oxidase and therefore, the inhibition of the normal degradation of purines. Aminopterin showed inhibition of thymidine protective effects toward adenine-treated cells. A synergistic effect, exerted by aminopterin and adenine is suggested to be the factor that inhibited thymidine protective effects on Drosophila adenine-treated cells and resulted in their death. The studies done with Hep-2 cells were used to compare the results of the present study with those already found in human cell lines.