Elevation of 8-Hydroxydeoxyguanosine in DNA from Isolated Mouse Lung Cells Following In Vivo Treatment with Aflatoxin B1

Abstract

Aflatoxin B(1) (AFB(1)) is a mycotoxin produced by some strains of Aspergillus and is a recognized pulmonary and hepatic carcinogen. The most widely accepted mechanism of AFB(1) carcinogenicity involves bioactivation to AFB(1)-8,9-exo-epoxide and binding to DNA to form AFB(1)-N(7)-guanine. Another potential cause of DNA damage is AFB(1)-mediated stimulation of reactive oxygen species formation, leading to oxidation of DNA bases. The objective of this study was to determine the ability of AFB(1) to cause oxidative DNA damage in lung cell types of the A/J mouse. The formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in freshly isolated mouse lung alveolar macrophages, alveolar type II cells, and nonciliated bronchial epithelial (Clara) cells was assessed by high-performance liquid chromatography with electrochemical detection. An approximately 3-fold increase in 8-OHdG formation occurred in both alveolar macrophage and Clara cell preparations isolated from A/J mice 2 h following treatment with a single tumorigenic dose of 50 mg/kg AFB(1) ip (n = 3, p < 0.05). Prior treatment with 300 kU/kg polyethylene glycol-conjugated catalase prevented the AFB(1)-induced increase in 8-OHdG levels in all mouse lung cell preparations (n = 3, p < 0.05). These results support the possibility that oxidative DNA damage in mouse lung cells contributes to AFB(1) carcinogenicity.

In vitro studies on chemoprotective effect of borax against aflatoxin B1-induced genetic damage in human lymphocytes

“…Among various aflatoxins, aflatoxin B1 (AFB1) is the most potent carcinogen ever tested (Umarani et al 2008). AFB1 is produced by some strains of Aspergillus and ingestion of aflatoxin-contaminated food and feed is known to cause hepatotoxicity, teratogenicity, immunotoxicity and even death in farm animals and humans (Guindon et al 2007). The mechanism of cellular damage caused by AFB1 has not been fully elucidated but reactive oxygen species (ROS) and lipid peroxidation (LPO) have been considered to be main mechanisms in the toxicity of AFB1 (Rastogi et al 2001;Shon et al 2004).…”

Boric acid: a potential chemoprotective agent against aflatoxin b1 toxicity in human blood

“…Among various aflatoxins, Aflatoxin B 1 (AFB 1 ) is the most potent carcinogen ever tested (Umarani et al 2008). AFB 1 is produced by some strains of Aspergillus and ingestion of aflatoxincontaminated food and feed is known to cause hepatotoxicity, teratogenicity, immunotoxicity and even death in farm animals and humans (Guindon et al 2007). The mechanism of cellular damage caused by AFB 1 has not been fully elucidated (Rastogi et al 2001).…”

Impacto das Fumonisinas, Aflatoxinas e Ocratoxina A na Avicultura

“…A mutação somática no gene TP53 está intimamente associada ao risco de desenvolver câncer de fígado, sugerindo que mecanismos dependentes da p53 normalmente agem para preservar a integridade genômica (KIRK et al, 2005). Adicionalmente, a AFB 1 pode atuar como alquilante do DNA resultando na formação de sítios apurínicos devido à perda de bases nitrogenadas, e, pode induzir à formação de espécies reativas de oxigênio (ROS) as quais promovem a oxidação do DNA (CHU; SAFFHIL, 1983;GUIDON;BERDARD;MASSEY, 2007).…”