The mutagenicity of kojic acid was studied by means of reversion mutation test in bacteria (Ames test), forward mutation test in cultured Chinese hamster cells and dominant lethal test in mice. A positive result was obtained only in Ames test (TA 98, 1535 and 100) which was not modified by the presence of S-9 fraction. Thus, it is concluded that although kojic acid is a weak mutagen in bacteria, it is nonmutagenic in eukaryotic systems either in vivo or in vitro.
Evidence that MC-induced dominant lethal mutations in early spermatids are attributable to chromosome aberrations was obtained through cytogenetic analysis of first-cleavage metaphases.Male mice were intravenously injected with 5 mg/kg of mitomycin C (MC). These males were serially mated with females during 6 weeks after treatment.Chromosome slides were prepared from eggs collected from the ampulla. The maximum frequencies of chromosome aberrations in male pronuclei in the eggs were obtained in early spermatid stages. A close correlation between the frequency of eggs with chromosome aberrations and that of dominant lethal mutations at the same dose was observed.
Male mice were treated with graded doses of methyl methanesulfonate (MMS) and mated with untreated female mice during the six to ten days after treatment. The nature of the primary lesions induced in late spermatids was investigated by analysing the types and rates of chromosome aberrations in the first cleavage metaphases. The chromosome aberrations recovered at the first cleavage were predominantly of the chromosome-type. Their frequency increased exponentially with increasing dose of MMS. The results suggested that the nonenzymatic conversion of DNA containing alkylated bases to new damage, possibly strand breaks, during the maturation and storage of sperm was primarily responsible for the enhancement of the frequency of chromosome-type aberrations.
The spermicidal activities of seven nonionic surfactants against human spermatozoa were objectively determined by a statistical method, and two types of ionic surfactants were also studied for purposes of comparison. The nonionic surfactants, p-menthanylphenyl polyoxethylene adducts used in this work were synthesized from turpentine oil. These surfactants were used in the experiment after a careful confirmation of their chemical composition and molecular weight distribution. The spermicidal activities of the surfactants in terms of minimum concentrations to accomplish irreversible immobilization of all sperms in zero time was, in decreasing order, nonionic, cationic and anionic. When the most commonly used nonionics alone were considered, the sequence of decreasing spermicidal potency was isononylphenyl polyoxyethylene (9.0) ether (nonoxynol-9), p-menthanylphenyl polyoxyethylene (8.8) ether (menfegol), isooctylphenyl polyoxyethylene (9.0) ether (octoxynol-9). The surface tension and wetting time of these surfactants were determined with a view to finding physico-chemical measures of their spermicidal activity. In the statistical analysis regarding all the nine surfactants, there was a significant correlation (p less than 0.05) between spermicidal potency and critical micelle concentration (cmc) whereas there was no significant relationship between spermicidal potency and cmc regarding the seven nonionics. There was again no significant correlation between spermicidal potency and wetting time in all but nonionics with a common hydrophobic structure. As neither surface tension nor wetting time appeared to be a valid factor, general measure of spermicidal potency of nonionic surfactants, the partition ratios between n-octanol or n-hexane and water was determined. As a result, it was revealed that there was a significant correlation (p less than 0.05) between spermicidal potency and partition coefficient, when four types of nonionic surfactants with different hydrophobic group, which were chosen from among the seven nonionics, were tested with n-hexane. The close relationship between spermical activity and partition coefficient suggests that the spermicidal activities of these surfactants are associated with their structural affinity to the lipids of spermatozoal cell membrane.
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