Mutagenicity tests with trypaflavin and hexamethylenetetramine in mammals in vivo and in vitro

Abstract

In our experiments we first tested the ability of different concentrations of trypaflavine and hexamethylenetetramine to induce dominant lethal mutations by injecting the compounds intraperitoneally or orally into male mice. Only for high dosages the induction of dominant lethals could be ascertained (50 mg trypaflavine per kg body weight and 25000 mg/kg hexamethylenetetramine). No specific sensitivity of single stages of the cycle of spermatogenesis was observed. It could be demonstrated by fluorescence microscopy that trypaflavine invades the male germ cells. Further indications for the weak mutagenicity of this compound we received cytogenetically by finding some chromosome aberrations and increased rates of univalents in diakinesis. In vitro investigations with hexamethylenetetramine in high final concentrations used in the mice experiments induced cell death, depression of mitosis and clumping of chromosomal material in blood cells as well as in HeLa cell cultures. Lower concentrations tested on HeLa cells were found to induce a number of chromosomal aberrations, but in a certain dosage, only (1×10-3M). No chromosome changes could be recognized in blood or HeLa cell mitosis when hexamethylenetetramine was given in final concentrations 1×10-4M and lower. A comparison of the used concentrations of the test substances and their mutagenic efficiency with the usual therapeutic dosages give rise to assume that the genetic risk for man is low for both drugs.