Antigenotoxic properties of lactic acid bacteria in the S. typhimurium mutagenicity assay

A high percentage of human tumors is reported to be related to dietary habits. One way to improve the nutritional impact is to increase the intake of protective factors, such as inhibitors of DNA damage and other types of anticarcinogens. Specific strains of lactic acid bacteria used to ferment milk are promising candidates that may be antimutagenic and anticarcinogenic. We have studied the antimutagenicity of 10 isolated strains of beneficial lactic acid bacteria. Four types of fermented milk products were also studied for their protective properties. The effect of these bacteria on the yield of revertants induced by nitrosated beef extract was investigated in the Salmonella typhimurium mutagenicity assay. Eight of 10 isolated Lactobacillus strains reduced the yield of his+ revertants almost back to the levels of the untreated controls. Different fermented fresh yogurts containing viable bacteria (probably Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus or Lactobacillus acidophilus and Bifidobacteria) showed protective effects as well. The degree of suppressing revertants was independent of the yogurt's fat content. In contrast, yogurt products that had been heat treated were not inhibitory. The other fresh fermented milk products (e.g., buttermilk, kefir, and “Dickmilch”) were not antimutagenic in this study. The results imply that some bacteria used in milk processing have an antimutagenic potential and that this property is specific for the bacterial strain.     

Mosaic mice with teratocarcinoma-derived mutant cells deficient in hypoxanthine phosphoribosyltransferase

Mutagenized stem cells of a cultured mouse teratocarcinoma cell line were selected for resistance to the purine base analog 6-thioguanine. Cells of a resistant clone were completely deficient in activity of the enzyme hypoxanthine phosphoribosyltransferase (HPRT, IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8), the same X-linked lesion as occurs in human Lesch-Nyhan disease. After microinjection into blastocysts of another genetic strain, the previously malignant cells successfully participated in normal embryogenesis and tumor-free, viable mosaic mice were obtained. Cells of tumor lineage were identified by strain markers in virtually all tissues of some individuals. Mature function of those cells was evident from their tissue-specific products (e.g., melanins, liver proteins). These mutagenized teratocarcinoma cells are therefore developmentally totipotent. Retention of the severe HPRT deficiency in the differentiated state was documented in extracts of mosaic tissues by depressed specific activity of the enzyme, and also by presence of unlabeled clones in autoradiographs of explanted cells incubated in [(3)H]hypoxanthine. Some mosaic individuals had mutant-strain cells in only one or a few tissues. Such animals may provide unique opportunities to identify the tissue sources of particular aspects of the complex disease syndrome. The tissue distribution of HPRT-deficient cells suggests that selection against them is particularly strong in blood of the mosaic mice, as is already known to be the case in human heterozygotes. This phenotypic parallelism supports the expectation that afflicted F(1) male mice that might be obtained from mutant germ cells can serve as a model of the human disease.     

Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas

Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions.