Transplacental carcinogenicity of low doses of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone administered subcutaneously or intratracheally to hamsters

Schüller, Hildegard M.; Jorquera, Rossana; Lu, Xiaoying; Riechert, A.; Castonguay, André

doi:10.1007/bf01372556

Cited by 18 publications

(13 citation statements)

References 3 publications

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“…Fifty-five proven carcinogens have been found in cigarettes, including polycyclic aromatic hydrocarbons, N-nitrosamines, aromatic amines, heterocyclic aromatic amines, aldehydes, aza-arenes, other organic compounds and inorganic compounds (Hecht, 1999). Of these, N-nitroso compounds are the most likely candidate transplacental liver carcinogens (Anderson et al, 1989;Correa et al, 1990;Beebe et al, 1993;Schuller et al, 1993Schuller et al, , 1994Hecht, 1998). These compounds can cross the human placenta, and their metabolites have been found both in the urine and bound to the fetal haemoglobin of newborns whose mothers smoked cigarettes (Coghlin et al, 1991;Lackmann et al, 1999) and in the fetus in early pregnancy (Milunsky et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

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

2003

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There are strong a priori reasons for considering parental smoking behaviour as a risk factor for childhood cancer but case -control studies have found relative risks of mostly only just above one. To investigate this further, self-reported smoking habits in parents of 3838 children with cancer and 7629 control children included in the United Kingdom Childhood Cancer Study (UKCCS) were analysed. Separate analyses were performed for four major groups (leukaemia, lymphoma, central nervous system tumours and other solid tumours) and more detailed diagnostic subgroups by logistic regression. In the four major groups, after adjustment for parental age and deprivation there were nonsignificant trends of increasing risk with number of cigarettes smoked for paternal preconception smoking and nonsignificant trends of decreasing risk for maternal preconception smoking (all P-values for trend 40.05). Among the diagnostic subgroups, a statistically significant increased risk of developing hepatoblastoma was found in children whose mothers smoked preconceptionally (OR ¼ 2.68, P ¼ 0.02) and strongest (relative to neither parent smoking) for both parents smoking (OR ¼ 4.74, P ¼ 0.003). This could be a chance result arising from multiple subgroup analysis. Statistically significant negative trends were found for maternal smoking during pregnancy for all diagnoses together (Po0.001) and for most individual groups, but there was evidence of under-reporting of smoking by case mothers. In conclusion, the UKCCS does not provide significant evidence that parental smoking is a risk factor for any of the major groups of childhood cancers. There are strong a priori reasons for considering parental smoking behaviour as a risk factor for childhood cancer. 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;. This effect has been attributed to germ-cell mutations during spermatogenesis caused by tobacco products (Wyrobeck, 1993;Wyrobek and Adler, 1996;Woodall and Ames, 1997). Relevant studies are reviewed by Thornton and Lee (1998).The United Kingdom Childhood Cancer Study (UKCCS) is a nationwide population-based...

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Section: Discussionmentioning

confidence: 99%

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

2003

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“…Low doses of these nitrosamines induce pancreatic tumors in rats, in addition to lung tumors (Hecht, 1998). Pancreatic tumors are also observed in the offspring of pregnant rats treated with NNK, and this effect is markedly enhanced by ethanol (Schu¨ller et al, 1993).…”

Section: Tobacco Smoke Carcinogens and Cancermentioning

confidence: 99%

Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers

et al. 2002

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It is estimated that cigarette smoking kills over 1 000 000 people each year by causing lung cancer as well as many other neoplasmas. p53 mutations are frequent in tobaccorelated cancers and the mutation load is often higher in cancers from smokers than from nonsmokers. In lung cancers, the p53 mutational patterns are different between smokers and nonsmokers with an excess of G to T transversions in smoking-associated cancers. The prevalence of G to T transversions is 30% in smokers' lung cancer but only 12% in lung cancers of nonsmokers. A similar trend exists, albeit less marked, in laryngeal cancers and in head and neck cancers. This type of mutation is infrequent in most other tumors aside from hepatocellular carcinoma. At several p53 mutational hotspots common to all cancers, such as codons 248 and 273, a large fraction of the mutations are G to T events in lung cancers but are almost exclusively G to A transitions in non-tobacco-related cancers. Two important classes of tobacco smoke carcinogens are the polycyclic aromatic hydrocarbons (PAH) and the nicotine-derived nitrosamines. Recent studies have indicated that there is a strong coincidence of G to T transversion hotspots in lung cancers and sites of preferential formation of PAH adducts along the p53 gene. Endogenously methylated CpG dinucleotides are the preferred sites for G to T transversions, accounting for more than 50% of such mutations in lung tumors. The same dinucleotide, when present within CpGmethylated mutational reporter genes, is the target of G to T transversion hotspots in cells exposed to the model PAH compound benzo[a]pyrene-7,8-diol-9,10-epoxide. As summarized here, a number of other tobacco smoke carcinogens also can cause G to T transversion mutations. The available data suggest that p53 mutations in lung cancers can be attributed to direct DNA damage from cigarette smoke carcinogens rather than to selection of pre-existing endogenous mutations.

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“…Cotinine and NNAL are known to readily pass through the placenta into the foetal circulation [23,24]. This most likely explains the high correlations between maternal and neonatal analyte levels in our population.…”

Section: Discussionmentioning

confidence: 95%

“…Maternal transmission of NNK to foetal mice has been demonstrated and can cause tumours, including malignant tumours that appear as the mice offspring mature [23,24]. Although there are conflicting reports, some human epidemiology studies suggest that exposure to tobacco smoke during pregnancy or during infancy is associated with an increased risk of cancer later in life [25,26].…”

Section: Discussionmentioning

confidence: 99%

Urine 4-(methylnitrosamino)-1-(3) pyridyl-1-butanol and cotinine in Alaska native postpartum women and neonates comparing smokers and smokeless tobacco users

Benowitz

Flanagan

Thomas

et al. 2018

International Journal of Circumpolar Health

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Objective: Foetuses and neonates of women who use tobacco are exposed to nicotine and tobacco-derived carcinogens. We determined the relationship between urine biomarkers of tobacco toxicant exposure postpartum and in the neonates of Alaska Native (AN) women, comparing smokers and smokeless tobacco (ST) users, including iqmik, a homemade ST product.Methods: AN women, including 36 smokers, 9 commercial ST and 16 iqmik users their neonates participated. Urine from the woman at the time of delivery and her neonate’s first urine were analysed for cotinine, the major metabolite of nicotine, and 4-(methylnitrosamino)-1-(3) pyridyl-1-butanol (NNAL), a tobacco-specific carcinogen biomarker.Results: Maternal urine cotinine and neonatal urine cotinine were strongly correlated in all tobacco use groups (r from 0.83 to 0.9, p < 0.002). Correlations between maternal cotinine and neonatal NNAL were moderately strong for cigarettes and commercial smokeless but weaker for iqmik users (r 0.73, 0.6 and 0.36, respectively).Conclusion: Correlations between maternal and neonatal biomarkers of tobacco toxicant exposure vary, dependent on tobacco product use.Significance: This study provides novel data on biomarkers of tobacco exposure among postpartum AN women and their neonates. The results could be useful to guide future epidemiological studies of health risks associated with use of various tobacco products during pregnancy.

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Transplacental carcinogenicity of low doses of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone administered subcutaneously or intratracheally to hamsters

Cited by 18 publications

References 3 publications

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

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

Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers

Urine 4-(methylnitrosamino)-1-(3) pyridyl-1-butanol and cotinine in Alaska native postpartum women and neonates comparing smokers and smokeless tobacco users

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