7 day low level dose response study of MelQx in rats using accelerator mass spectroscopy

2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) is a heterocyclic amine that forms in meats during cooking and has been shown to cause cancer in laboratory animals at high doses. Structurally, MelQx belongs to a class of heterocyclic amines often referred to as amino-imidazoazaarenes or AlA's. MelQx, like all AlA-type compounds, is highly mutagenic in the Ames/Salmonella microsome-mediated assay, having a potency, depending on the bacterial tester strain, between 56,000 and 99,000 revertants/ug (Felton and Knize 1990). MelQx is also mutagenic in mammalian cell systems. Long-term feeding studies in mice (0.06% MelQx in diet) show an 43% and 99% incidence of liver tumors in male and female CDF1 mice, respectively (Ohgaki 1987). In F344 rats continuously fed MelQx (0.04% in diet for 429 days) the incidence of liver tumors was 100% and 53% for males and females, respectively (Kato 1988). A high incidence of zymbal gland tumors in males and females, as well as clitoral gland tumors in female rats, were also found. The authors report here on the use of accelerator mass spectrometry (AMS) to trace the absorption, distribution, and elimination of human-relevant levels of [14C]MeIQx given to animals. The authors also report on the relationship between DNA binding and administered dose using [14C]-MeQIx