Mutagenicity Of Anabolic-Androgenic Drugs After Nitrite Treatment

Mahidol University Annual Research Abstracts. inhibition of the catalytic activities of cytochrome P-450 system of phase I. The lowest dose of 4-hexylresorcinol increased number of revertants of the final reaction product when it was added along with AP and nitrite. The increase may due to the stimulation on mutagen formation during acid incubation via the mechanism of C-nitroso formation. Whereas, 4-hexylresorcinol may act as a nitrite scavenger at the higher doses.

Anabolic-androgenic steroid drugs (AAS drugs) abuse by athletes is wide spread at present. Doping of athletes with drugs presumed to enhance athletic ability. Under a gastric condition, using a megadose of drugs for a long time will cause an interaction with nitrite, which is used as food preservative and additive in many food stuffs. Furthermore, many mutagenic products are produced by reaction of their precursors in foods with nitrite under this condition. Thus, effects of AAS drugs during mutagenic formation and on mutagenic product were studied by using the represented AP-nitrite model.

Six often abused AAS drugs namely: danazol, fluoxymesterone, mesterolone, methandienore, stanozolol, and testosterone unTradtionalnoate were evaluated for mutagenicity themselves and after nitrite treatment in the pH like gastric condition (pH 3-3.5) using the Salmonella mutagenicity assay (Ames test) without metabolic activation. No mutagenicity of both AAS drugs themselves and nitrite treated products was found. The interaction between nitrite treated aminopyrene (AP) and each drug gave rise to some modulating effects. It was found that stanozolol and fluoxymesterone enhanced the mutagenicity to both TA98 and TA100 while testosterone unTradtionalnoate did only on TA98.

On the other hand, danazol decreased the mutagenicity of nitrite treated AP on both tester strains TA98 and TA100 while mesterolone and methandienone did not show any clear results. Furthermore, inhibitory effects on mutagenic product were found in all drugs except methandienone on both tester strains. In conclusion, AAS drugs did not show mutagenicity in the Ames Salmonella assay. However, their effect on mutagenicity of AP-nitrite model did not give clear results. Due to the unclear results of these drugs with nitrite found in many food stuffs, they should be avoided with or after meals. In fact, these drugs should be used only in the emergency situations to control diseases.



The Salmonella / microsome mutager city test according to Ames et al. was performed in order to detect possible mutagenicity of repeated deep fi-jing fat fractions of two edible oils, palm oil and rice bran oil, after repeated fiying of potatoes, lean pork meat and sausages. Furthermore, the mutagenicity of oil- nitrite mixture a:fter repeated heating without food were investigated. The Ames assay was carried out without metabolic activation The results show no mutagenic effects of the fractions of deep fiying fats nor of the oil-riitrite mixture. However, the evaluation of fried and raw sausage samples in simulated gastric condition showed that mutagenic activity. Was present only in the sample containing enough sodium nitrite to react with some precursors in heated oil for mutagen formation.

Many agricultural chemicals contain structures that can interact with nitrite and produce carcinogenic compounds. In Thailand, organophosphate insecticide residues are frequently detected but not often exceed the Codex Maximum Residue limits (Codex MRLs) and may result as precursors of mutagens after coming into contact with nitrite in the stomach. Hence, the main aim of this study was to determine the mutagenic potential of organophosphate insecticides treated with nitrite. It was also determined the modifying effects of these insecticides on the mutagen formed during aminopyrene-nitrite reaction and on the final product of 4-h incubation of aminopyrine-nitrite reaction in an acid solution using Ames assay with Salmonella typhimurium strains TA98 and TA100 in the absence of metabolic activation.

The results showed that formulated products of organophosphate insecticides namely; dimethoate, malathion, palathion and methamidophos treated with nitrite were not mutagenic toward both.





 

 

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