PhIP (2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) is one of the most abundant heterocyclic amines (HCAs) in cooked meat. PhIP is formed at high temperatures from the reaction between creatine or creatinine (found in muscle meats), amino acids, and sugar. PhIP formation increases with the temperature and duration of cooking and also depends on the method of cooking and the variety of meat being cooked. The U.S. Department of Health and Human Services National Toxicology Program has declared PhIP as "reasonably anticipated to be a human carcinogen". International Agency for Research on Cancer (IARC), part of World Health Organization, has classified PhIP as IARC Group 2B carcinogen (i.e., possibly carcinogenic to humans). There is sufficient evidence in experimental animals, as well as in vitro models, for the carcinogenicity of PhIP.
Sources of PhIP
PhIP has been found in cooked beef, pork, chicken, and fish products. Exposure to PhIP depends on the eating habits of the individual and can vary up to 5000-fold. Exposure is also related to the type of meat, doneness, cooking method, and quantity consumed. Individual exposures can differ due to various anti-carcinogens in the diet. Different cooking methods for meat (broiling, grilling, frying, roasting, pan drippings) all contribute to formation of PhIP.
PhIP and cooking methods
Studies examining the amount of PhIP in cooked meats have shown that high levels of exposure are possible. Doneness levels of meat (rare, medium, well-done, and very well-done) are factors in the development of PhIP. Methods to reduce formation of PhIP in meats include decreasing the temperature at which the meat is cooked, decreasing the length of cooking time, pre-heating meat in the microwave oven (which reduces creatine), and marinating the meat.
Dietary intake of PhIP
Determining dietary intake of PhIP can be obtained by more or one ways. One method used is a Food Frequency Questionaries (FFQ) which surveys a population on their estimated consumption of cooked meats. Another method directly measures the quantity of PhIP in a cooked meat sample. However, because the formation of PhIP in cooked meat items is dependent on temperature, cooking time, and cooking method, variations do occur in the direct measurement method. Direct measurement methods have determined dietary intake levels of PhIP to range from 0.07-4.3 ng/kg per day.
Associated cancers
Numerous
in vivo and
in vitro studies have demonstrated that PhIP is a potent
mutagen and can induce tumors of multiple sites in animal models. PhIP was positive in bacterial (
Ames) test and induced chromosomal abnormalities in human and Chinese hamster cells
in vitro. PhIP has also formed
DNA adducts in vivo in both rats and monkeys.
[18] PhIP has been tested for carcinogenicity in both mice and rats by oral administration. Increases in
lymphomas were seen in mice and increases in
adenocarcinomas of the small and large intestine in males and mammary
adenocarcinomas in female were seen in rats. Also, an increasing number of
epidemiological studies have evaluated the association of well-done meat intake and HCA exposure with cancer risk in humans. In general, these studies have reported that high intake of well-done and/or high exposure to PhIP may be associated with cancer of the colorectum, breast, prostate, pancreas, lung, stomach, and esophagus.
PhIP has been shown to induce
DNA adducts and mutations. These
adducts have been found in a wide variety of sensitive tissues and organs such as the colon. However,
adducts also formed in sites that did not commonly form tumors, such as the kidneys. In humans receiving a dose of PhIP equivalent to that found in very well-done chicken,
DNA and protein
adducts were formed in the colon and blood. However, the
adducts were unstable and declined over a 24 hour period.
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