In utero–initiated cancer: The role of reactive oxygen species

Abstract

It is becoming more evident that not only can drugs and environmental chemicals interfere with normal fetal development by causing structural malformations, such as limb defects, but that xenobiotic exposure during development can also cause biochemical and functional abnormalities that may ultimately lead to cancer later on in life. Fetal toxicity may be partly mediated by the embryonic bioactivation of xenobiotics to free radical intermediates that can lead to oxidative stress and potentially lead, in some cases, to carcinogenesis. Using a number of examples, this review will focus on the role of reactive oxygen species (ROS) in the mechanisms pertaining to in utero initiated cancers.

Maternal Smoking and the Risk of Cancer in Early Life – A Meta-Analysis

“…Cigarette smoke contains more than 5300 constituents and according to IARC, for 70 of them there is sufficient evidence for carcinogenicity in laboratory animals or humans [5]. Placental barrier with transporter proteins, as well as xenobiotic metabolism of the mother, the unborn child and the placenta determine the exposure of the offspring to different chemicals [8, 102]. …”

“…Animal models using Syrian hamster showed transplacental carcinogenesis caused by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone exposure. It is one of the IARC Class I carcinogens in cigarette smoke, and it has been detected in urine of newborns of smoking mothers, indicating a direct exposure of the unborn child to the carcinogen [102]. Another constituent of cigarette smoke, nicotine, causes the addictive characteristics of cigarettes.…”

“…Whichever error occurs during DNA duplication, in that time period such an error will manage to be imprinted in the DNA of a high number of subsequent cells. These errors might not directly lead to cancer, but can increase the susceptibility of cells to later insults of carcinogens [102]. …”

Polish mother and child cohort study — defining the problem, the aim of the study and methodological assumptions

“…Some authors implicated the important role of oxidative stress and insufficient antioxidant level/activity in aetiology of premature delivery, eclampsia, intrauterine growth retardation, congenital malformations and developmental abnormalities in surviving offspring [22,23]. Imbalance in antioxidant status during the prenatal and early postnatal periods may affect individual's future life.…”

“…Imbalance in antioxidant status during the prenatal and early postnatal periods may affect individual's future life. Oxidative stress has been suggested to be involved in the pathogenesis of several chronic diseases, including atherosclerosis, inflammatory diseases, cancer, and certain neurological disorders [22,24]. There is a lot of evidences that cellular bioavailability of bioactive compounds depends on individual susceptibility, which may be attributable to inherited genetic predispositions related to genetic polymorphisms of many genes [25].…”