Transfer of the tobacco-specific carcinogens N′-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo [a] into the milk of lactating rats

Abstract

The extent to which some of the more prevalent and potent carcinogens in cigarette smoke could be transferred from circulating blood into the milk of lactating rats was determined. One hour after i.v. administration of benzo[a]pyrene (BaP), N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to the dams, the levels of these carcinogens were determined in both blood and milk specimens. The average amount of radioactivity detected 1 h after administration of 14C-labeled BaP was 0.21% of the administered dose per ml of milk as compared with 0.17% per ml of blood. The amount of NNN in milk ranged from 0.20 to 0.36% of the administered dose per ml which closely paralleled the levels detected in blood. NNK is readily converted in vivo to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). The sum of NNK and NNAL was similar in the blood and milk of treated dams. There was, however, a major difference in the ratio of NNAL/NNK as detected in milk and blood. The ratio of NNAL/NNK in blood ranged from 1.3:1 to 1.9:1 while the ratio in milk ranged from 2.4:1 to 3.3:1. In a comparative study of the levels of NNN in the blood and milk of lactating rats at less than 1.0, 20, 60, 120 and 240 min after administration, it was confirmed that similar concentrations of NNN are present in blood and milk 1 h after administration. These data indicate that these carcinogens, which are present in both cigarette smoke and tobacco, can be transferred into the milk of lactating rats.

Passive exposure to electronic cigarette aerosol in pregnancy: A case study of a family

“…Tobacco-specific carcinogens also can be transferred to milk, as shown in animal models (LaVoie et al, 1987;Zanieri et al, 2007), but we did not find nitrosamines and other toxicants in our sample, and they were not detected in maternal samples, either. 1,2-PD was not detected in breast milk, and we found lower levels of metals in breast milk when compared with other studies of recent mothers from the general population (non-users of e-cigarettes or conventional cigarettes) (Freire et al, 2022;Szukalska et al, 2021), with the exception of copper and zinc, which were present in higher concentrations than in a Spanish population (Motas et al, 2021).…”

Interception of reactive, DNA adduct‐forming metabolites present in rodent serum following carcinogen exposure: Implications for use of body fluids in biomonitoring

“…The noncovalent interaction between carrier proteins and lipophilic compounds enhances metabolite stability in the serum by providing protection from an otherwise hydrolytic, aqueous environment [43]. Serum albumin and lipoproteins are known to form physical but noncovalent complexes with several carcinogens and/or their metabolites such as BP, 3-methylcholanthrene, 4-(methy1nitrosoamino)-1-(3-pyridy1)-1 -butanone (NNK), and dimethylaminoazobenzene [43][44][45][46][47]. A variety of other lipophilic compounds including a-carotene, lycopene, dolichole and @-tocopherol have also been found to interact noncovalently with lipoproteins in human serum [48].…”

Haemoglobin adducts as biomarkers of exposure to tobacco-related nitrosamines

“…Many of these compounds are not only carcinogenic when applied directly to animals, but also have considerable teratogenicity to pregnant rats and mice (Reckzeh et al 1975). Two classes of chemicals found in tobacco which appeared to be most widely recognized as being both carcinogenic as well as toxic include the tobacco-specific nitrosamines as well as the polycyclic aromatic hydrocarbons (LaVoie et al 1987, Rodriguez et al 1999, Joseph et al 2005. Both of these classes of compounds have been clearly demonstrated to give rise to animal tumours of a variety of types upon exposure or inhalation and it is widely regarded that these classes of compounds potentially play a role in the aetiology of human cancers caused by exposure to tobacco (Haustein 1999, Nelson 1999b.…”

“…The tobacco-specific nitrosamines NNN (N'-nitrosonornicotine) and NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) are the most potent carcinogens in tobacco smoke and smokeless tobacco products. These nitrosamines induce tumours of the lung, liver, nasal cavity and pancreas in the rat and are implicated in potential human carcinogenesis caused by tobacco exposure (LaVoie et al 1987, Hoffmann et al 1991. NNK is metabolically activated to a reactive species that binds covalently to haemoglobin and to DNA and as a result these covalent modifications can be accessed by cleavage and the resulting released product characterized using mass spectrometric tools .…”