Relative genotoxic activities of pesticides evaluated by a modified SOS microplate assay

Abstract

The genotoxic activities of 47 pesticides were determined using a modified SOS microplate assay in which the induction of beta-galactosidase in E. coli PQ37 was used as a quantitative measure of genotoxic activity. The results were compared with those obtained with anethole, curcumin, and capsaicin, a few examples of naturally occurring compounds present in foods. The assays were conducted with pesticides dissolved either in a suitable solvent, such as 10% DMSO in physiological saline or dispersed in sodium taurocholate micelles, to simulate conditions in the small intestine from where these substances are normally absorbed from the diet. 4-Nitroquinoline oxide (4-NQO) served as the reference standard of a direct acting mutagen. In micellar form, 4-NQO and 25 of the 47 pesticides tested showed significantly higher genotoxic activities than when they were tested in an organic solvent. In micellar form the SOS inducing potency of 4-NQO was almost twice as high as in 10% DMSO in physiological saline. In taurocholate micelles, the five most active compounds had activities in the range of 1,234-3,765 units/mumol and in the order of decreasing activities they were ranked as follows: malathion > dichlorvos > lindane > chlordane > endrin. They were significantly less active than 4-NQO (less than 40%). In micellar solution the naturally occurring compounds, anethole, curcumin, and capsaicin gave activities of 4,594, 928, and 809 units/mumol, respectively. These studies show that genotoxicity may depend upon the environment in which cells are exposed to these potential genotoxins. It appears that testing of the more hydrophobic compounds, both synthetic and naturally occurring, are needed.

Identification of biomarkers that distinguish human papillomavirus (HPV)-positive versus HPV-negative head and neck cancers in a mouse model

“…To assess the contributions of HPV16 E6 and E7 in HNSCC, we employed a strategy previously used to induce oral and esophageal cancers in nontransgenic mice (31). This strategy makes use of 4NQO, a carcinogen that, although not a natural tobacco derivative, causes a spectrum of DNA damage similar to that caused by tobacco-derived carcinogens (26)(27)(28)(29)(30). Groups of HPV16-transgenic (K14E6͞K14E7) mice and nontransgenic mice were treated for 16 weeks with 4NQO dissolved in their drinking water at a dose 1͞10th of that used in the previous study (31).…”

“…Because tobacco use is implicated in HNSCC, we monitored cancers in K14E6͞K14E7 doubly transgenic mice treated with the chemical carcinogen, 4-nitroquinoline 1-oxide (4NQO). 4NQO causes a spectrum of DNA damage similar to that caused by tobacco-associated carcinogens (26)(27)(28)(29)(30), and it induces cancers of the oral cavity in rodents when it is supplied in their drinking water (31). 4NQO-treated, HPV16-transgenic mice developed HNSCC at a much higher frequency than nontransgenic mice.…”

Induction of Apoptosis in Leukemic Cells by Homovanillic Acid Derivative, Capsaicin, through Oxidative Stress

“…Spicy foods may play some role in human carcinogenesis, and to date one single epidemiological study has demonstrated that there was a correlation between hot chilli pepper consumption and incidence of gastric cancer (2); however, other studies have failed to provide evidence for its genotoxic potential (3,4). Capsaicin extracts have been extensively investigated for their effects on genotoxicity and mutagenicity in vitro as well as in vivo, but the study results are conflicting (5)(6)(7).…”

Oral Cavity Carcinogenesis Modeled in Carcinogen-Treated Mice

“…4NQO is a water-soluble quinoline derivative that can cause DNA adduct formation, resulting in adenosine substitution for guanosine [26][27][28] . 4NQO may also undergo redox cycling to produce reactive oxygen species that result in mutations and DNA strand breaks 29,30) .…”