amounts of carcinogens, because the gastrointestinal tract protects itself against carcinomas by shedding its outer layer continuously. Furthermore, detoxification enzymes, such as cytochromes P450 have increased activities in the gut for protection from food-borne toxins. Thus, in most cases, small amounts of BaP are metabolized prior to being passed into the blood. The lungs are not protected in either of these manners. The detoxification enzymes cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) are both protective and necessary for benzo[a]pyrene toxicity. Experiments with strains of mice engineered to remove (knockout) CYP1A1 and CYP1B1 reveal that CYP1A1 primarily acts to protect mammals from low doses of BaP, and that removing this protection accumulates large concentrations of BaP. Unless CYP1B1 is also knocked out, toxicity results from the bioactivation of BaP to benzo[a]pyrene -7,8-dihydrodiol-9,10-epoxide, the ultimate toxic compound,. Interaction with DNA Properly speaking, BaP is a procarcinogen, meaning that its mechanism of carcinogenesis depends on its enzymatic metabolism to BaP diol epoxide It intercalates in DNA, and the electrophilic epoxide is attacked by nucleophilic guanine bases, forming a bulky guanine adduct. X-ray crystallographic and nuclear magnetic resonance structure studies have shown how this binding distorts the DNA by confusing the double-helical DNA structure. This disrupts the normal process of copying DNA and causes mutations, which explains the occurrence of cancer after exposure. This mechanism of action is similar to that of aflatoxin which binds to the N7 position of guanine. There are indications that benzo[a]pyrene diol epoxide specifically targets the protective p53 gene. This gene is a transcription factor that regulates the cell cycle and hence functions as a tumor suppressor. By inducing G (guanine) to T (thymidine) transversions in transversion hotspots within p53, there is a probability that benzo[a]pyrene diol epoxide inactivates the tumor suppression ability in certain cells, leading to cancer. Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide is the carcinogenic product of three enzymatic reactions: Benzo[a]pyrene is first oxidized by cytochrome P450 1A1 to form a variety of products, including (+)benzo[a]pyrene-7,8-epoxide. This product is metabolized by epoxide hydrolase, opening up the epoxide ring to yield (−)benzo[a]pyrene-7,8-dihydrodiol. The ultimate carcinogen is formed after another reaction with cytochrome P450 1A1 to yield the (+)benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide. It is this diol epoxide that covalently binds to DNA. BaP induces cytochrome P450 1A1 (CYP1A1) by binding to the AHR (aryl hydrocarbon receptor) in the cytosol. Upon binding the transformed receptor translocates to the nucleus where it dimerises with ARNT (aryl