Carcinogens target site

Those that scavenge active molecular species of carcinogens to prevent their reaching critical target sites in the cell... 

Thus, the biochemical changes associated with exposure to carcinogens have been studied in detail, and consequently, the target site and the interactions of carcinogens with it is more clearly understood than in other areas of toxicology. 

Amino groups Decreased lipophilic character Increased water solubility due to salt formation. Decreased lipid solubility. Provides a new centre for hydrogen bonding, which could influence the binding of the drug to the target site. The incorporation of aromatic amines is avoided as they are often toxic and/or carcinogenic. 

Animal studies provide convincing evidence that BDCM is carcinogenic. BDCM caused cancer at lower doses and at more target sites than for any of the other THMs. In a 2 year bioassay, a corn oil gavage study, compound-related tumors were found in the liver, kidneys, and large intestine in rats. However, only renal and hepatic tumors were evident in mice. 

Various mathematical models have been developed to explore the implications for dose-response relations of what is known about carcinogenicity mechanisms. Under some sets of assumptions consistent with these mechanisms, the risk of neoplastic transformation at low doses is directly proportional to the target site dose. This is the so-called straight-line, or linear, model of dose-response a picture of it is presented in the next chapter. 

Unlike polycyclic aromatic hydrocarbons, nitrosamines require only the first activation step which forms a hydroxylated intermediate that is sufficiently unstable to spontaneously decompose and generate a reactive carbonium which can rapidly alkylate target macromolecules in the cell. In contrast, nitrosamides do not require metabolic activation because of inherent chemical instability in aqueous solution. Nitrosamides decompose at physiological pH nonenzymatically to produce the same class of reactive electrophiles as the nitrosamines. Although the actual target site for nitroso carcinogens is not yet elucidated, a number of alkylation sites in DNA are known such as 0 -CH3-G, 7-CH3-G, and 3-CH3-A (2). 

First, they must be able to reach target sites at sufficiently high level. As discussed earlier, the physicochemical properties of the chemical play a determining role. Reactive direct-acting electrophilic chemicals are often potent carcinogens if they are either... 

Detoxification of organophosphorus pesticides before they can reach their target sites is probably the main reason for poor correlation between carcinogenicity and electrophilicity/mutagenicity. The problem is further complicated by the fact that several different enzymes are involved in the metabolic detoxification of organophosphorus pesticides. For example, paraoxon, tetrachlojTvinphos and dimethoate are preferentially detoxified by A-esterase (paraoxonase), GSH-dependent S-alkyltransferase and carboxyesterase (aliesterase), respectively whereas chlorfenvinphos is mainly detoxified by NADPH-dependent oxidative dealkylation... 

C stands for carbocation formation during the attack of the ultimate carcinogen on the DNA target sites. 

For a PAHDE to be carcinogenic it must have a reasonable lifetime to permit selective, specific and persisted interaction(s) with DNA. Activation near or at the target site is certainly the most effective means of generating potent carcinogens at a sufficiently high level. Still there are ample chances of detoxification either by its covalent binding to inhibitors or hydrolysis to inactive tetraols. 

Supplements that are antioxidants, scavenging free radicals before they reach target sites and initiate carcinogenesis. These componnds also activate enzymes that break down carcinogens, reducing them to harmless compounds. 

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