Metabolism of 2-aminofluorene by human polymorphonuclear leukocytes: more evidence for the association between inflammation and cancer.

Abstract

Recent investigations have demonstrated the ability of leukocytes to metabolize promutagens or procarcinogens into their genotoxic forms. As a possible explanation for the association between inflammation and cancer, we and others have hypothesized that local accumulations of leukocytes could take up nearby promutagens, metabolize them, and release genotoxic agents that may cause damage in the surrounding tissue. Using a modified, two-step preincubation protocol with Salmonella, we have tested this hypothesis. We have shown that total human peripheral blood leukocytes, cultured in the presence of 2-aminofluorene for 18 hr, can metabolize 2-aminofluorene into agents mutagenic to Salmonella typhimurium strain TA98. Furthermore, experiments in which polymorphonuclear leukocytes were separated from mononuclear leukocytes demonstrated that the PMNs metabolized 2-aminofluorene to a much greater extent than the MNs.

Physical and chemical interactions between bile pigments and polyaromatic mutagens

“…88,90 Therefore, Bhosale et al 88 suggested that experiments involving in 1.3 (PRO) should be performed in the dark to avoid the formation of photooxidation products. [105][106][107] It is important to note that 1.5 (2AF) is oxidized by cytochrome P450 enzymes to the more active electrophilic agent, N-hydroxy-2-aminofluorene (N-OH-2-AF) and then HOSO 2 O-NH-2-AF under the action of sulfotransferase or N-acyltransferase. They are both considered the most likely to attack the nucleophilic positions in DNA such as C8-arylamine-dG, C8-arylamine-dA, and the amino group of deoxyguaninosine as depicted in Figure 1 The level of 1.8 (PhIP) in food varies greatly depending on type of food and cooking method.…”