Increased risk of cancer in the descendants of syrian hamsters exposed prenatally to diethylnitrosamine (DEN)

Möhr, U.; Emura, M.; Kamino, Kenji; Steinmann, J.; Köhler, Manfred; Morawietz, Gerd; Dasenbrock, Clemens; Tomatis, Lorenzo

doi:10.1002/ijc.2910630116

Cited by 13 publications

(5 citation statements)

References 13 publications

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“…Rats, mice and Syrian hamsters, exposed once to a carcinogen, gave birth to tumorous descendents in three succeeding generations, and sensitivity to carcinogens increased (Druckrey et al 1970;Tomatis 1994;Mohr et al 1995). These reports reinforce Fig.…”

Section: Resultssupporting

confidence: 62%

Paragenetic suppressors of suppressor genes - a new class of oncodeterminants

Roushdy

Michel

Petry

et al. 1999

Journal of Cancer Research and Clinical Oncology

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Impairment or loss of suppressor genes is a common event permitting the oncogene/suppressor gene machinery to develop neoplasia. Following prenatal treatment with X-rays and UV-B, we detected a new class of oncodeterminants that could not be specified as genes. This points to paragenetic elements that suppress suppressorgenes and thus provoke melanoma at earlier ages of onset as expected, with increased severity and increased number of incidences in successive generations, in the absence of further treatment. These elements were isolated from a xiphophorine DNA library by endogenously labeled long terminal repeats (LTR) of a xiphophorine retrovirus, and were characterized as retrotransposons by Southern and Northern blotting and reverse transcription/polymerase chain reaction and transient transfection studies, in situ hybridization, and sequencing. They appear in multiple copies in the telomeric chromosome regions, where they can extend. Three open reading frames (ORF) are flanked by LTR that contain genetically active regulatory elements, and are inducible by UV-B. ORF 3 shows nests of CG dinucleotides and CGG trinucleotides, which are reminiscent of CGG nests predisposing subjects to anticipation of certain human diseases involving tumor generation. Genetic anticipation as defined by Nettleship (1909) or Warren (1996) including an increase of neoplasia might represent an acquired genetic load in preceding generations, which might provide a lead to a molecular understanding of the worldwide increase of incidences of human tumor.

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Section: Resultssupporting

confidence: 62%

Paragenetic suppressors of suppressor genes - a new class of oncodeterminants

Roushdy

Michel

Petry

et al. 1999

Journal of Cancer Research and Clinical Oncology

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“…Effects have also been noted after transplacental exposure of mouse fetuses to DES, with mid-gestation, late-gestation, and neonatal treatment having similar effects on the incidence of vaginal tumors in the F2 descendants (146). Female hamster fetuses were less sensitive than their brothers to a multigenerational effect of transplacental NDEA, with a significant effect noted only after exposure on day 13 (145).…”

Section: Animal Models Preconceptional/transgenerationai Effectsmentioning

confidence: 94%

Critical windows of exposure for children's health: cancer in human epidemiological studies and neoplasms in experimental animal models.

Anderson

Diwan

Fear

et al. 2000

Environ Health Perspect

269

153

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In humans, cancer may be caused by genetics and environmental exposures; however, in the majority of instances the identification of the critical time window of exposure is problematic. The evidence for exposures occurring during the preconceptional period that have an association with childhood or adulthood cancers is equivocal. Agents definitely related to cancer in children, and adulthood if exposure occurs in utero, include: maternal exposure to ionizing radiation during pregnancy and childhood leukemia and certain other cancers, and maternal use of diethylstilbestrol during pregnancy and clear-cell adenocarcinoma of the vagina of their daughters. The list of environmental exposures that occur during the perinatal/postnatal period with potential to increase the risk of cancer is lengthening, but evidence available to date is inconsistent and inconclusive. In animal models, preconceptional carcinogenesis has been demonstrated for a variety of types of radiation and chemicals, with demonstrated sensitivity for all stages from fetal gonocytes to postmeiotic germ cells. Transplacental and neonatal carcinogenesis show marked ontogenetic stage specificity in some cases. Mechanistic factors include the number of cells at risk, the rate of cell division, the development of differentiated characteristics including the ability to activate and detoxify carcinogens, the presence of stem cells, and possibly others. Usefulness for human risk estimation would be strengthened by the study of these factors in more than one species, and by a focus on specific human risk issues.ImagesFigure 1

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“…Single treatments with 50 mg/kg bw on GD 14 or 15 were without effect (Diwan and Meier, 1976 ). The F1 generation of Syrian hamsters developed tumours in the respiratory tract when mothers were treated with 5 mg/kg bw or more on 1 or more days in the second half of the gestational period (Mohr and Althoff, 1965 ; Mohr et al, 1966 , 1975 , 1995 ). Similar to reports on NDMA, at certain gestational periods, the fetus was susceptible to postnatal development of respiratory tract tumours.…”

Section: Assessmentmentioning

confidence: 99%

“…Similar to reports on NDMA, at certain gestational periods, the fetus was susceptible to postnatal development of respiratory tract tumours. Interestingly, lymphoma, uterine carcinoma and laryngotracheal neuroendocrine tumours occurred at an increased frequency in the F2-generation deriving from F1-animals that had been treated on GD13 or GD14 (Mohr et al, 1995). Following a single s.c. application of 100 mg/kg bw to dams, the compound was present for at least 2 h in maternal blood, placenta, fetus and amniotic fluid of the hamsters (Althoff et al, 1977) For NDPA data on developmental effects and transplacental carcinogenesis derive from one group studying the compound in Syrian Golden hamster.…”

Section: Nmampa and Nmambamentioning

confidence: 99%

Risk assessment of N‐nitrosamines in food

Schrenk¹,

Bignami²,

Bodin³

et al. 2023

EFS2

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EFSA was asked for a scientific opinion on the risks to public health related to the presence of Nnitrosamines (N-NAs) in food. The risk assessment was confined to those 10 carcinogenic N-NAs occurring in food (TCNAs), i.e. NDMA, NMEA, NDEA, NDPA, NDBA, NMA, NSAR, NMOR, NPIP and NPYR. N-NAs are genotoxic and induce liver tumours in rodents. The in vivo data available to derive potency factors are limited, and therefore, equal potency of TCNAs was assumed. The lower confidence limit of the benchmark dose at 10% (BMDL 10 ) was 10 μg/kg body weight (bw) per day, derived from the incidence of rat liver tumours (benign and malignant) induced by NDEA and used in a margin of exposure (MOE) approach. Analytical results on the occurrence of N-NAs were extracted from the EFSA occurrence database (n = 2,817) and the literature (n = 4,003). Occurrence data were available for five food categories across TCNAs. Dietary exposure was assessed for two scenarios, excluding (scenario 1) and including (scenario 2) cooked unprocessed meat and fish. TCNAs exposure ranged from 0 to 208.9 ng/kg bw per day across surveys, age groups and scenarios. 'Meat and meat products' is the main food category contributing to TCNA exposure. MOEs ranged from 3,337 to 48 at the P95 exposure excluding some infant surveys with P95 exposure equal to zero. Two major uncertainties were (i) the high number of left censored data and (ii) the lack of data on important food categories. The CONTAM Panel concluded that the MOE for TCNAs at the P95 exposure is highly likely (98-100% certain) to be less than 10,000 for all age groups, which raises a health concern.

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Increased risk of cancer in the descendants of syrian hamsters exposed prenatally to diethylnitrosamine (DEN)

Cited by 13 publications

References 13 publications

Paragenetic suppressors of suppressor genes - a new class of oncodeterminants

Paragenetic suppressors of suppressor genes - a new class of oncodeterminants

Critical windows of exposure for children's health: cancer in human epidemiological studies and neoplasms in experimental animal models.

Risk assessment of N‐nitrosamines in food

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