There is good evidence that the complex microbial flora present in the gastrointestinal tract of all warm-blooded animals is effective in providing resistance to disease. However, the composition of this protective flora can be altered by dietary and environmental influences, making the host animal susceptible to disease and/or reducing its efficiency of food utilization. What we are doing with the probiotic treatments is re-establishing the natural condition which exists in the wild animal but which has been disrupted by modern trends in conditions used for rearing young animals, including human babies, and in modern approaches to nutrition and disease therapy. These are all areas where the gut flora can be altered for the worse and where, by the administration of probiotics, the natural balance of the gut microflora can be restored and the animal returned to its normal nutrition, growth and health status.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2672.1989.tb05105.x

Probiotics in man and animals

The human diet contains a great variety of natural mutagens and carcinogens, as well as many natural antimutagens and anticarcinogens. Many of these mutagens and carcinogens may act through the generation of oxygen radicals. Oxygen radicals may also play a major role as endogenous initiators of degenerative processes, such as DNA damage and mutation (and promotion), that may be related to cancer, heart disease, and aging. Dietary intake of natural antioxidants could be an important aspect of the body’s defense mechanism against these agents. Many antioxidants are being identified as anticarcinogens. Characterizing and optimizing such defense systems may be an important part of a strategy of minimizing cancer and other age-related diseases.

https://science.sciencemag.org/content/sci/221/4617/1256.full.pdf

Dietary carcinogens and anticarcinogens Oxygen radicals and degenerative diseases

Probiotics are usually defined as microbial food supplements with beneficial effects on the consumers. Most probiotics fall into the group of organisms' known as lactic acid-producing bacteria and are normally consumed in the form of yogurt, fermented milks or other fermented foods. Some of the beneficial effect of lactic acid bacteria consumption include: (i) improving intestinal tract health; (ii) enhancing the immune system, synthesizing and enhancing the bioavailability of nutrients; (iii) reducing symptoms of lactose intolerance, decreasing the prevalence of allergy in susceptible individuals; and (iv) reducing risk of certain cancers. The mechanisms by which probiotics exert their effects are largely unknown, but may involve modifying gut pH, antagonizing pathogens through production of antimicrobial compounds, competing for pathogen binding and receptor sites as well as for available nutrients and growth factors, stimulating immunomodulatory cells, and producing lactase. Selection criteria, efficacy, food and supplement sources and safety issues around probiotics are reviewed. Recent scientific investigation has supported the important role of probiotics as a part of a healthy diet for human as well as for animals and may be an avenue to provide a safe, cost effective, and 'natural' approach that adds a barrier against microbial infection. This paper presents a review of probiotics in health maintenance and disease prevention.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2672.2006.02963.x

Probiotics and their fermented food products are beneficial for health.

Genistein, found in soy products, is a phytochemical with several biological activities. In the current study, our research focused on the estrogenic and proliferation-inducing activity of genistein. We have demonstrated that genistein enhanced the proliferation of estrogen-dependent human breast cancer (MCF-7) cells in vitro at concentrations as low as 10 nM, with a concentration of 100 nM achieving proliferative effects similar to those of 1 nM estradiol. Expression of the estrogen-responsive gene pS2 was also induced in MCF-7 cells in response to treatment with a concentration of genistein as low as 1 microM. At higher concentrations (above 20 microM), genistein inhibits MCF-7 cell growth. In vivo, we have shown that dietary treatment with genistein (750 ppm) for 5 days enhanced mammary gland growth in 28-day-old ovariectomized athymic mice, indicating that genistein acts as an estrogen in normal mammary tissue. To evaluate whether the estrogenic effects observed in vitro with MCF-7 cells could be reproduced in vivo, MCF-7 cells were implanted s.c. in ovariectomized athymic mice, and the growth of the estrogen-dependent tumors was measured weekly. Negative control animals received the American Institute of Nutrition (AIN)-93G diet, the positive control group received a new s.c. estradiol (2 mg) pellet plus the AIN-93G diet, and the third group received genistein at 750 ppm in the AIN-93G diet. Tumors were larger in the genistein (750 ppm)-treated group than they were in the negative control group, demonstrating that dietary genistein was able to enhance the growth of MCF-7 cell tumors in vivo. Increased uterine weights were also observed in the genistein-treated groups. In summary, genistein can act as an estrogen agonist in vivo and in vitro, resulting in the proliferation of cultured human breast cancer cells (MCF-7) and the induction of pS2 gene expression. Here we present new information that dietary genistein stimulates mammary gland growth and enhances the growth of MCF-7 cell tumors in ovariectomized athymic mice.

https://cancerres.aacrjournals.org/content/canres/58/17/3833.full.pdf

Estrogenic Effects of Genistein on the Growth of Estrogen Receptor-positive Human Breast Cancer (MCF-7) Cells in Vitro and in Vivo

Inhibitory Effect of Yogurt on Ehrlich Ascites Tumor-Cell Proliferation

The entire second thoracic mammary glands of 4-week-old BALB/c female mice primed with oestradiol plus progesterone were cultivated in organ culture medium containing the 'growth-promoting' hormone combinations: insulin, prolactin, growth hormone, oestradiol, progesterone and aldosterone or insulin, prolactin and aldosterone. Full lobulo-alveolar development was induced after 5–6 days of incubation and could be maintained for 15–16 days in organ culture in medium containing either hormone combination. After the initial 5–6 days in the 'growth-promoting' medium, subsequent cultivation of the glands in a medium with the 'lactogenic hormones', insulin, prolactin plus cortisol, led to accumulation of 'milk-like' secretory material in the ductal and alveolar lumina. Incubation of the lobulo-alveolar gland in medium with insulin alone for 7–9 days resulted in complete regression of the alveoli leaving only a ductal parenchyma. Incubation in insulin, prolactin, growth hormone or insulin plus the steroid hormones for 7–9 days led to considerable alveolar degeneration without a complete regression. The results indicate that both pituitary and steroid hormones are essential for development and maintenance of mammary alveoli; insulin can only sustain the basal ductal structure.

Hormonal regulation of lobulo-alveolar growth, functional differentiation and regression of whole mouse mammary gland in organ culture.

Organ culture of whole mammary gland of the mouse

Biological characteristics of nodule-like alveolar lesions (NLAL) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in organ culture of whole mammary gland (BALB/c female mice) were assessed after transplantation into gland-free mammary fat pads of syngeneic virgin mice. (i) Tissue-fragment explants from NLAL areas of the gland produced abnormal lobuloalveolar (LA) outgrowths in 3 of 10 fat pads. (ii) Transplantation of dissociated cells of NLAL-derived LA outgrowths into 36 fat pads showed 100% LA outgrowths and 3 (8%) of these 36 outgrowths produced mammary carcinomas. (iii) The explants of dissociated cells from whole mammary glands treated with DMBA in culture produced full or partial LA structures in 2 of 56 outgrowths. (iv) The explants of dissociated cells prepared from outgrowths derived from outgrowths derived from explants as in iii produced 9 LA outgrowths in 16 instances; mammary tumor incidence in these outgrowths was 3 of 16 (18%). (v) The explants of tissue fragments from LA outgrowths as in iv produced LA outgrowths in 20 of 20 fat pads; mammary carcinomas appeared in 16 of 20 (80%) of these outgrowths. No NLAL was detectable in control glands treated with dimethyl sulfoxide (solvent for DMBA); explants of the control glands consistently produced ductal outgrowths and no tumor. This accomplishment of chemical carcinogen-induced neoplastic transformation of epithelial cells in vitro provides a model for studying carcinogenesis in an entire isolated organ.

/pdf/neoplastic-transformation-of-epithelial-cells-in-whole-4ldze04r3i.pdf

Neoplastic transformation of epithelial cells in whole mammary gland in vitro

Epidemiological studies have suggested that β-carotene, a dietary vitamin A precursor, may influence reduced tumor incidence in human populations1. In contrast to the abundance of studies2,3 on the chemopreventive properties of retinoids (vitamin A analogues) little is known about the mode of action of β-carotene, the vitamin A precursor. Only a few preliminary reports based on rather indirect observations have indicated that a carrot rich diet or injections of β-carotene result in reduced tumor incidence in rats and mice treated with a carcinogenic chemicals and/or u.v. radiation4–6. These observations prompted the investigations of the chemopreventive role of β-carotene itself in an in vitro controlled environment, because in the animal the vitamin A precursor is metabolized to retinol.

Mihir R. Banerjee

Papers

Inhibitory Effect of Yogurt on Ehrlich Ascites Tumor-Cell Proliferation

Hormonal regulation of lobulo-alveolar growth, functional differentiation and regression of whole mouse mammary gland in organ culture.

Organ culture of whole mammary gland of the mouse

Neoplastic transformation of epithelial cells in whole mammary gland in vitro

β-Carotene Prevention of 7,12-Dimethylbenz [A] Anthracene-Induced Transformation of Mouse Mammary Cells In Vitro