modifies the microenvironment (e.g., stromal cells) of potential cancer-causing lung epithelial cells (if neoplastically transformed), researchers investigated whether low-dose-gamma rays could modify the in vitro response of stromal cells to BPDE
When BaP enters our body, it is synthesized to create BPDE
. This compound then binds to our genes, making it difficult for them to function effectively.
reacts chemically with DNA, forming a very tight bond at the nucleobase guanine.
IL6 promoter SNPs and the effects of [H.sub.2][O.sub.2] and BPDE
on IL-6 secretion in human fibroblasts.
Figure-1 shows the reaction and diffusion of chemical compound BPDE
in different subdomains of the cell.
The steps include generation of benzo(a)pyrene-7,8-epoxide, benzo(a)pyrene-7,8-diol, and finally benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE
Although B[a]P was metabolized to BPDE
in HCC cells, to what extent BPDE
mediates the effects of B[a]P on HCC progression remains unknown.
Investigation of BPDE
elimination has been largely restricted to in vitro and in vivo studies of rodents.
The protocols were harmonized and adjusted in an interlaboratory comparison study among the three [sup.32]P-postlabeling investigator laboratories, including the use of the same external benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE
)-DNA standard [111 adducts in [10.sup.8] normal nucleotides (nt), which was a kind gift from F.F.
Several toxicologic studies have suggested that benzo[a]pyrene diolepoxide (BPDE
), a biologically reactive metabolite of PAH, inhibits DNA methylation.
Carcinogenesis requires metabolic activation by enzymes, including the cytochrome P450 (CYP)1 family, which generates DNA adduct-forming products of some PAHs, including the BaP metabolite BaP-7,8-dihydrodiol-9, 10-epoxide (BPDE
) (Shimada and Fujii-Kuriyama 2004).
We calculated the tetraol concentrations by comparing the samples analyzed with an external calibration curve, generated from the fluorescence peak of a known amount of authentic benzo[a]pyrene diol epoxide (BPDE
) tetraol standard, every time a set of samples was analyzed.