Heterocyclic aromatic amines and their contribution to the bacterial mutagenicity of the particulate phase of cigarette smoke

Abstract

Heterocyclic aromatic amines (HAAs) rank among the strongest known mutagens. Approximately 30 HAAs have been found in cooked foods (broiled, fried, and grilled) and several HAAs have been characterized as animal carcinogens. Nine HAAs have also been reported to be constituents of cigarette smoke (CS) raising concerns that HAAs might contribute significantly to the known carcinogenicity of CS. As HAAs are found predominantly in the total particulate matter (TPM) of CS, an improved method for the quantification of HAAs in TPM is reported allowing detection and quantification of 8 HAAs in a single run. The mutagenic potency of these HAAs and that of TPM from the reference cigarette 2R4F was determined in the Salmonella Reverse Mutation Assay (Ames assay) with tester strain TA98 and a metabolic activation system. The 8 HAAs, when applied together in the Ames assay, showed a clear sub-additive response. Likewise, the combination of HAAs and TPM, if at all, gave rise to a slight sub-additive response. In both cases, however, the sub-additive response in the Ames assay was observed at HAA doses that are far above the amounts found in CS. The contribution of the individual HAAs to the total mutagenic activity of TPM was calculated and experimentally confirmed to be approximately 1% of the total mutagenic activity. Thus, HAAs do not contribute significantly to the bacterial in vitro mutagenicity of CS TPM.

Alterations in the nigrostriatal dopamine system after acute systemic PhIP exposure

“…It is worth noting that the doses used there are 2,000 – 40,000 times higher than the average human consumption (5 – 50 ng/kg daily). However, humans consume numerous HCAs (~30 known, likely many unknown) vs. PhIP alone, suggesting that considering dietary intake of a single HCA underestimates total HCA consumption (Augustsson et al , 1997; Roemer et al , 2016). Further, our previous studies found that of the two primary metabolic pathways, the N -hydroxylation product is far more neurotoxic than ring-hydroxylation (Griggs et al , 2014).…”

Selective dopaminergic neurotoxicity of three heterocyclic amine subclasses in primary rat midbrain neurons

“…Although the examples above indicate that several HCAs are potentially neurotoxic, there is a significant gap in the literature with respect to tested neurotoxicity (Griggs et al , 2014; Ichinose et al , 1988). Importantly, to date, there have been roughly ~30 HCAs found to be present in the diet, with many more likely that are currently unknown (Roemer et al , 2016), and these compounds vary broadly in structural and physical properties, as well as mutagenicity (Felton et al , 1999; Kawamori et al , 2004; Layton et al , 1995; Totsuka et al , 2004). Our goal here was to test HCAs from three important subclasses that are found in the diet.…”

Determination of 14 heterocyclic aromatic amines in meat products using solid‐phase extraction and supercritical fluid chromatography coupled to triple quadrupole mass spectrometry

“…These chemicals can be produced during cooking . Different conditions can affect the formation of HAs during cooking, such as pH, the cooking time, temperature, content of water, and water‐soluble materials . In recent years, the harm of HAs to human health is a great concern of issue .…”

“…Besides, in biological samples (such as serum, hair, bile, human milk, urine, and so on), HAs have been detected . Even in many environmental samples (such as rain, water, air, cigarette smoke, and so on), HAs residues have also been reported . Considering the harm of these mutagens, it is necessary to develop sensitive and selective methodologies to quantify these compounds.…”