Mutational spectrum of dimethylnitrosamine in the liver of 3- and 6-week-oldlacI transgenic mice

Boer, Johan G. de; Mirsalis, Jon C.; Glickman, Barry W.

doi:10.1002/(sici)1098-2280(1999)34:2/3<80::aid-em4>3.0.co;2-4

Cited by 9 publications

(1 citation statement)

References 18 publications

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“…Information on the mutagenicity of NDMA in whole animals came from several studies in lacZ or lacI C57BL/6 and B6C3F1 transgenic mice (Mirsalis et al, 1993 ; Tinwell et al, 1994 ; Suzuki et al, 1996 ; Souliotis et al, 1998 ; De Boer et al, 1999 ; Shane et al, 2000 ). Good agreement of positive and negative results was observed among the different TransGenic Rodent (TGR) assays (reviewed in Lambert et al, 2005 ).…”

Section: Assessmentmentioning

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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Section: Assessmentmentioning

confidence: 99%

Risk assessment of N‐nitrosamines in food

Schrenk¹,

Bignami²,

Bodin³

et al. 2023

EFS2

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Mammary glands of sexually immature rats are more susceptible than those of mature rats to the carcinogenic, lethal, and mutagenic effects of N‐nitroso‐N‐methylurea

Ariazi

Haag

Lindstrom

et al. 2005

Molecular Carcinogenesis

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Knowing that the prepubertal period is a time of enhanced susceptibility for radiation-induced human breast cancer, we used the Fischer 344 rat model to explore the age-differential susceptibility of the mammary gland to the carcinogenic, lethal, and mutagenic effects of two structurally diverse chemical carcinogens, N-nitroso-N-methylurea (NMU), and 7,12-dimethylbenz(a)anthracene (DMBA). Mammary carcinoma incidences and multiplicities were significantly greater in immature than mature NMU-treated rats while mammary carcinoma incidences and multiplicities were significantly lower in immature than mature DMBA-treated rats. The survival of mammary clonogens of mature NMU-treated rats in limiting dilution transplantation assays was greater than that of the survival of mammary clonogens of immature NMU-treated rats. No differences were found in the survival of mammary cells from immature and mature rats exposed to DMBA. Although there were no mutation spectra differences, mammary epithelial cells of immature NMU-treated rats had greater mutation frequencies than those of mature NMU-treated rats. Together these results support the hypothesis that the mammary gland of immature rats is more susceptible to the carcinogenic, lethal, and mutagenic effects of alkylating agents represented by NMU in a carcinogen-class-specific manner. Further, the results suggest the importance of mechanistic and epidemiological studies of the susceptibility of the prepubertal breast to specific carcinogens such as alkylating agents.

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Evaluation of Plant Extracts in Mammalian Systems: Applications of the Big Blue® Rodent Mutational Assay

Boer

2001

Development of Plant-Based Medicines: Conservation, Efficacy and Safety

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Mutational spectrum of dimethylnitrosamine in the liver of 3- and 6-week-oldlacI transgenic mice

Cited by 9 publications

References 18 publications

Risk assessment of N‐nitrosamines in food

Risk assessment of N‐nitrosamines in food

Mammary glands of sexually immature rats are more susceptible than those of mature rats to the carcinogenic, lethal, and mutagenic effects of N‐nitroso‐N‐methylurea

Evaluation of Plant Extracts in Mammalian Systems: Applications of the Big Blue® Rodent Mutational Assay

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