Benzo(a)pyrene - Toxicity

Toxicity

A vast number of studies over the previous three decades have documented links between benzopyrene and cancers. It has been more difficult to link cancers to specific benzopyrene sources, especially in humans, and difficult to quantify risks posed by various methods of exposure (inhalation or ingestion). Researchers at Kansas State University recently discovered a link between vitamin A deficiency and emphysema in smokers. Benzopyrene was found to be behind the link, since it induces vitamin A deficiency in rats.

In 1996, a study was published that provided the clear molecular evidence conclusively linking components in tobacco smoke to lung cancer. Benzopyrene, found in tobacco smoke (including cigarette smoke), was shown to cause genetic damage in lung cells that was identical to the damage observed in the DNA of most malignant lung tumours.

A 2001 National Cancer Institute study found levels of benzopyrene to be significantly higher in foods that were cooked well-done on the barbecue, particularly steaks, chicken with skin, and hamburgers. Japanese scientists showed that cooked beef contains mutagens, chemicals that are capable of altering the chemical structure of DNA. However, the foods themselves are not necessarily carcinogenic, even if they contain trace 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 due to the normal requirement for protection from food-borne toxins. Thus in most cases small amounts of benzopyrene are metabolized by gut enzymes prior to being passed on to the blood. The lungs are not protected in either of these manners.

A recent study has found that cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) are both protective and, confusingly, necessary for benzopyrene 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 benzopyrene, and that removing this protection causes the biological accumulation of large concentrations of benzopyrene. Unless CYP1B1 is also knocked out, benzopyrene toxicity results from the bioactivation of benzopyrene to the ultimate toxic compound, benzopyrene -7,8-dihydrodiol-9,10-epoxide (see below).