Synthesis, characterization andIn vitro identification ofN 7-Guanine adduct of 2-bromopropane

Abstract

Recently, we have reported that 2-bromopropane might have an immunotoxic potential in rats when exposed for 28 days. In the present studies, the possibility of 2i-deoxyguanosine adduct formation by 2-bromopropane was investigated in vitro to elucidate molecular mechanism of 2-bromopropane-induced immunosuppression. N7-Guanine adduct of 2'-bromopropane (i.e., N7-isopropyl guanine) was chemically synthesized and structurally characterized by analysis of UV, 1H-NMR, '3C-NMR, COSY and fast atom bombardment mass spectrometry to use as a reference material. Incubation of 2'-deoxyguanosine with an excess amount of 2-bromopropane in PBS buffer solution, pH 7.4, at 37 degrees C for 16 h, followed by a thermal hydrolysis, produced a detectable amount of N7-isopropyl guanine by an HPLC and UV analysis. The present results suggest that 2-bromopropane might form a DNA adduct in N7 position of 2'-deoxyguanosine at a physiological condition.

Role of glutathione conjugation in the hepatotoxicity and immunotoxicity induced by 1‐bromopropane in female BALB/c mice

“…In addition, the DNA adduct of 1-BP could possibly be formed in hepatocytes or splenocytes. Evidence that 1-BP can lead to the formation of mercapturic acids and DNA adducts was suggested in the previous study (Zhao et al, 2002;Lee et al, 2003). The formation of N 7 -guanine adducts by 1-BP could be detected in an incubation of calf thymus DNA with 1-BP in physiological conditions, suggesting that the formation of DNA adducts might be related with 1-BP induced toxicity.…”

Effects of prenatal exposure to the environmental pollutant 2-bromopropane on embryo-fetal development in rats

“…Epidemiological studies suggested that 2-BP might be the causative agent of these health disorders (Kim et al, 1996;Park et al, 1997). Since the outbreak of reproductive disorders after exposure to 2-BP in Korea, several extensive animal studies have been conducted to determine the potential adverse effects of 2-BP on reproductive, hematopoietic, central nervous, and immune systems (Ichihara et al, 1997;Omura et al, 1999;Son et al, 1999;Wu et al, 2002;Yu et al, 1999;Zhao et al, 2002). Maeng and Yu (1997) reported that 2-BP exhibited no mutagenic effects on mouse bone marrow cells as determined by in vivo chromosome aberration and in vivo micronucleus tests, but Ishikawa et al (2001) showed an induction of micronuclei formation in preimplantation mouse embryos after maternal treatment with 2-BP accompanied by a decrease in embryo cell number.…”

Neuro-reproductive toxicities of 1-bromopropane and 2-bromopropane

“…Kaneko et al (1997) demonstrated that 2-bromopropane is less stable in water than 1-bromopropane, indicating also the tendency for SN1 reactions in polar solvents as mentioned above. Zhao et al (2002) investigated N7-adduct of guanine formed from 2-bromopropane and concluded that DNA adduct might be related to DNA damage although they did not examine other DNA adducts including O6-adduct of guanine. On the other hand, 1-bromopropane was found to reduce protein-bound sulfhydryl base ) and could form a covalent bond with cysteine residues of globin and other proteins in the spinal cord (Ichihara et al 2004a).…”

“…The authors considered DNA damage, impaired anti-oxidant defenses and lipid peroxidation to be responsible for the testicular toxicity of 2-bromopropane. Possible DNA damage was also suggested by DNA adduct formation by 2-bromopropane in vitro (Zhao et al 2002).…”