Detection of Smoking-Related Covalent DNA Adducts in Human Placenta

Abstract

The presence of covalent DNA chemical addition products (adducts) in human term placentas was investigated by recently developed immunologic and 32P-postlabeling assays. DNA from placental specimens of smokers showed a small but not statistically significant increase in adduct levels when tested by antibodies to DNA modified with a benzo[a]pyrene dihydrodiol epoxide (BPDE-I), the ultimate carcinogenic derivative of benzo[a]pyrene. The postlabeling assay detected several modified nucleotides, one of which (adduct 1) strongly related to maternal smoking during pregnancy. This adduct was present in placental tissue from 16 of 17 smokers, but only 3 of 14 nonsmokers. Among smokers, levels of adduct 1 in general were only weakly related to questionnaire and biochemical measures of the intensity of smoking exposures, which suggests modulation by individual susceptibility factors. The adduct seemed to be derived from an aromatic carcinogen, but it may not result from several of the most intensely studied polycyclic aromatic hydrocarbons or aromatic amines in tobacco smoke. The data show the association of cigarette smoking with covalent damage to human DNA in vivo.

Urothelial Carcinoma Associated with the Use of a Chinese Herb (Aristolochia fangchi)

“…The total adduct levels ranged from 1.7 to 175 per 10 9 normal (unaffected) nucleotides. In four patients who were long-term smokers, a diffuse band of radioactivity typical of smoking-related adducts (referred to as the diagonal radioactive zone) 21 was present in addition to the aristolochic acid-related DNA adducts (Fig. 1B).…”

Excretion of biliary compounds during intrauterine life

“…In contrast, drug-and toxin-induced upregulation of biotransforming enzymes can lead to an enhanced production of reactive metabolites able to interact with DNA, resulting in the formation of DNA adducts [142] . This may challenge the normal development of the conceptus.…”

Parental smoking and childhood cancer: results from the United Kingdom Childhood Cancer Study

“…Many proven carcinogens are present in tobacco and tobacco smoke (Hecht, 1999;Hoffmann and Hoffmann, 1997). Tobacco-related compounds have also been detected in human placenta, fetal blood, urine of offspring and in breast milk of smoking mothers (Perlman and Dannenberg, 1942;Everson et al, 1986Everson et al, , 1988Woodward et al, 1986;Hansen et al, 1992;Myers et al, 1996;Pinorini-Godly and Myers, 1996;Arnould et al, 1997;Daube et al, 1997).Previous case -control studies have tended to show weak associations between maternal cigarette smoking during pregnancy and childhood cancers (IARC, 1986;Severson et al, 1993;Tredaniel et al, 1994;Sorahan et al, 1995Sorahan et al, , 1997a Sorahan et al, , b, 2001Klebanoff et al, 1996;Shu et al, 1996). There is somewhat stronger and more consistent evidence for a paternal preconceptional effect, although relative risks in most case -control studies are only just above one (Severson et al, 1993;Shu et al, 1996;Ji et al, 1997;Sorahan et al, 1997b;.…”

“…Many proven carcinogens are present in tobacco and tobacco smoke (Hecht, 1999;Hoffmann and Hoffmann, 1997). Tobacco-related compounds have also been detected in human placenta, fetal blood, urine of offspring and in breast milk of smoking mothers (Perlman and Dannenberg, 1942;Everson et al, 1986Everson et al, , 1988Woodward et al, 1986;Hansen et al, 1992;Myers et al, 1996;Pinorini-Godly and Myers, 1996;Arnould et al, 1997;Daube et al, 1997).…”