Treatment with Mutagen

The above mentioned cell lines can be cloned under appropriate conditions in soft agar. Upon addition of high concentrations of a potent glucocorticoid, for example, dexamethasone at 0.1-1 /rM concentrations the vast majority of S49.1 or CEM-7 cells die but a few cells form colonies. These clones are completely resistant to the cytolytic hormone effect. Resistance is a stable heritable trait which arises randomly in the cell population treatment with mutagens increases the rate at which resistant cells come up [20,53]. 

In conclusion, the described yeast system is well suited for the secretory expression of small disulfide-bonded, non-glyco-sylated proteins. It should be emphasized that the performance of yeast cells for expression of a particular protein can be further optimized by conventional strain development programs using UV-irradia-tion or treatment with mutagenic compounds. 

Genes for resistance are not new creations. There seems to be no exception to the rule in genes responsible for resistance to macrolide antibiotics. In fact, many kinds of clinical isolates that carry resistant determinant(s) to macrolide antibiotics rarely develop the same mechanism as drug-resistant mutants, which arise in vitro from treatment with mutagens. 

Skare JA, Schrotel KR. 1984. Alkaline elution of rat testicular DNA Detection of DNA strand breaks after in vivo treatment with chemical mutagens. Mutat Res 130 283-294. 

Figure 4. Toxic and mutagenic response of diploid human lymphoblast line MIT-2 to aflatoxin B,. Open symbols afatoxin + phenobarbital-induced rat liver postmitochondrial supernatant (PMS) closed symbols effect of treatment with either aflatoxin or FMS alone.

Ames tests reveal that SOAz does not induce any mutagenicity at all, even with toxic doses (lOOy per plate and more) on any TA strain. This is a real — but fully unexpected — improvement on MYKO 63. We may in fact assume that patients cured by treatment with SOAz, will not have any further relapse. The origin of this absolute non-mutagenic behaviour has so far not been explained. 

Di(2-ethylhexyl) adipate did not bind covalently to mouse liver DNA in vivo. One report showed evidence of oxidative damage in rat liver DNA in vivo but not in rat kidney DNA. A weak dominant lethal effect has been reported in male mice. Analyses of mouse bone marrow after treatment with di(2-ethylhexyl) adipate in vivo found no induction of micronuclei in one study and no induction of chromosomal aberrations in one study. Urine from rats treated with di(2-ethylhexyl) adipate by gavage was not mutagenic to Salmonella typhimurium. 

A number of metabolic studies of 3,3 -dichlorobenzidine congener-based pigments (e.g., Cl Pigment Yellow 12,13,17, and 83), however, showed that these pigments are not broken down to release free dichlorobenzidine in animals, and they are not mutagenic in bacterial assays [35,36]. No increased tumor incidence was observed after treatment with Cl Pigment Yellow 12 in carcinogenesis bioassays in rats and mice [37]. 

Migliore, L., Cocchi, L. Scarpato, R. (1996) Detection of the centromere in micronuclei by fluorescence in situ hybridization its application to the human lymphocyte micronucleus assay after treatment with four suspected aneugens. Mutagen., 11, 285-290... 

Methyl chloride was mutagenic to bacteria and induced chromosomal aberrations in plants. It induced unscheduled DNA synthesis in cultured rat hepatocytes and, in rats exposed in vivo, there was a small increase in unscheduled DNA synthesis in hepatocytes but not in tracheal epithelial cells or spermatocytes. DNA strand breaks were induced by methyl chloride in the kidney cells of exposed mice. In cultured mammalian cells, it induced mutations and sister chromatid exchanges and enhanced viral cell transformation. It induced dominant lethal effects in rats. The last effect appears to be due to a failure of the males to fertilize the females, rather than to preimplantation embryonic death and can be partially inhibited by treatment with an anti-inflammatory agent (Chellman et al., 1986c). 

---