Polycyclic aromatic hydrocarbons and digestive tract cancers: a perspective

Abstract

Cancers of the colon are most common in the Western world. In majority of these cases, there is no familial history and sporadic gene damage seems to play an important role in the development of tumors in the colon. Studies have shown that environmental factors, especially diet, play an important role in susceptibility to gastrointestinal (GI) tract cancers. Consequently, environmental chemicals that contaminate food or diet during preparation become important in the development of GI cancers. Polycyclic aromatic hydrocarbons (PAHs) are one such family of ubiquitous environmental toxicants. These pollutants enter the human body through consumption of contaminated food, drinking water, inhalation of cigarette smoke, automobile exhausts, and contaminated air from occupational settings. Among these pathways, dietary intake of PAHs constitutes a major source of exposure in humans. Although many reviews and books on PAHs and their ability to cause toxicity and breast or lung cancer have been published, aspects on contribution of diet, smoking and other factors toward development of digestive tract cancers, and strategies to assess risk from exposure to PAHs have received much less attention. This review, therefore, focuses on dietary intake of PAHs in humans, animal models, and cell cultures used for GI cancer studies along with epidemiological findings. Bioavailability and biotransformation processes, which influence the disposition of PAHs in body and the underlying causative mechanisms of GI cancers, are also discussed. The existing data gaps and scope for future studies is also emphasized. This information is expected to stimulate research on mechanisms of sporadic GI cancers caused by exposure to environmental carcinogens.

Figure 1

Some representative PAH compounds

Figure 2

Schematic of B(a)P metabolism. From Ramesh et al (24); with permission.

Figure 3

A. Representative forestomach tumors (arrow) in BaP-treated mice. Mice were sacrificed at wk 16 (A, B) and wk 32 (D, E) after the first administration of benzo[a]pyrene (BaP) in control mice (A and D), BaP + IgG-treated mice (B and E). The size and volume of forestomach carcinoma is more compared to controls. From Chen et al (140); with permission. B. Representative tumors in the colon of Apc^Min mouse treated with (A) 50 mg B(a)P/kg body weight and (B) 100 mg B(a)P/kg bodyweight. Mice were sacrificed 60 days after exposure to B(a)P via oral gavage. The number of polyps increased with B(a)P in saturated fat compared to unsaturated fat. The tumors were located in the distal colon near the rectum and measured >5 mm. From Harris et al (124); with permission.

Figure 4

Histology of forestomach carcinoma in mice. Mice were sacrificed at wk 16 (A, B) and wk 32 (D,E) with their stomachs excised. The number of squamous cell carcinomas was increased in BaP + IgG-treated-mice. A and D: control mice; B and E: BaP + IgG-treated mice. From Chen et al (140); with permission.

Figure 5

Effects of Cyp1b1 deletion and DMBA treatment on the histology of Min tumors at days 55 and 130. Mice were sacrificed at either 55 d of age (A and B) or 130 d of age (C). Tumors were isolated from day 55 oil-treated Min and Cyp1b1-deficient Min control mice (A), day 55 DMBA-treated Min and Cyp1b1-deficient Min mice (B) Sections were stained with H&E (column 3 insets) or β-catenin (left), phospho-IKK (p-IKK; middle). From Halberg et al (152); with permission.

Figure 6

Pathology of polyps in the jejunum and colon and in liver tissue of an Apc^Min mouse treated with 100 μg B(a)P/kg bw for sixty days via oral gavage in saturated fat. Hematoxylin and eosin staining of the jejunum of control (A) mice (40×) show small adenomas with no high grade dysplasia. Jejunum of B(a)P-treated mice (B) [40×] show invasive carcinoma. The colons of control mice (C) [40×] show small adenomas with high-grade dysplasia, whereas colons of B(a)P-treated mice (D) [40×] show large adenoma with high-grade dysplasia. B(a)P, benzo(a)pyrene. From Harris et al (124); with permission.