potassium-bromide and Adenocarcinoma

Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activities for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes.

Topics: Adenocarcinoma; Administration, Oral; Animals; Bread; Bromates; Bromides; Carcinogenicity Tests; Carcinogens; Carcinoma, Renal Cell; Chromosome Aberrations; Cocarcinogenesis; Cricetinae; Cysteine; Dose-Response Relationship, Drug; Fish Products; Food Additives; Food Handling; Glutathione; Hair Preparations; Hearing Loss; Humans; Japan; Kidney Diseases; Kidney Neoplasms; Maximum Allowable Concentration; Mesocricetus; Mesothelioma; Mice; Mutagenicity Tests; Occupational Diseases; Peritoneal Neoplasms; Potassium; Potassium Compounds; Rats; Rats, Inbred F344; Species Specificity; Thyroid Neoplasms; United Kingdom; United States

The effects of KSCN and other chaotropic salts on the androgen receptor in cytosol of Shionogi carcinoma 115 were studied by means of charcoal adsorption assay and sucrose gradient centrifugation. When KSCN or NaSCN was added to the [3H]-dihydrotestosterone-cytosol mixture at the final concentration of 0.5 M, the androgen binding to the cytosol receptor was considerably inhibited. The inhibition reached maximum within 5 h at 0 degrees C and was dependent on the kind of chaotropic anion added: the potency of inhibitory effect in descending order was KSCN greater than KI greater than KBr greater than KCl. The inhibition was not observed in the estradiol-receptor interaction with KSCN or NaSCN up to 0.5 M. When 0.5 M KSCN-treated androgen-cytosol mixture was subjected to gel filtration or (NH4)2SO4 fractionation to remove the salt, a partial recovery (30-40%) in specific binding activity was observed. The binding activity of androgen receptor was unaffected by a treatment with KSCN up to 0.1 M and the androgen-receptor complex sedimented in a 5S form in 0.1-0.3 M KSCN, 0.5 M KCl or 0.5 M KBr. These results suggest that the binding activity of androgen receptor is more susceptible than that of estrogen receptor to chaotropic salts which cause impairment in intramolecular hydrophobic interactions.

Topics: Adenocarcinoma; Animals; Bromides; Centrifugation, Density Gradient; Cytosol; Dihydrotestosterone; Male; Mice; Neoplasms, Experimental; Potassium; Potassium Compounds; Potassium Iodide; Receptors, Androgen; Receptors, Steroid; Thiocyanates