Abstract
Recent studies have demonstrated the presence of DNA adducts from 4-aminobiphenyl (4-ABP) in the bladder cells of humans; however, the correlation between the concentration of these adducts and the tumorigenic response is not clear. To help elucidate this relationship, we have investigated DNA adduct formation in experimental animals continuously administered 4-ABP. Male and female BALB/c mice were treated for 28 days with 4-ABP. hydrochloride in their drinking water. DNA adducts in target tissues (liver of females and bladder of males) were identified and quantified by 32P-postlabeling analyses and radioimmunoassays. These results were compared to previously reported tumor incidences obtained from the lifetime administration of 4-ABP hydrochloride. The major adduct observed in both tissues was N-(deoxyguanosin-8-yl)-4-ABP. In the bladders of both sexes and the livers of female mice, adduct levels increased with dose at low doses, but saturation was observed at high doses. In the livers of males, the adduct levels were linearly correlated with dose throughout the entire dose range. A comparison between DNA adducts and tumorigenesis indicated a linear correlation between adduct levels and the incidence of liver tumors in female mice. In the bladders of male mice, however, the relationship was markedly nonlinear. These data suggest that adduct formation alone is insufficient for tumorigenesis in the bladder and that other factors such as cell proliferation are necessary for tumor production.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.