Increased incidence of abnormal foetuses in the offspring of cyclophosphamide-treated male mice

Jenkinson, P.C.; Anderson, Diana; Gangolli, S.D.

doi:10.1016/0165-1218(87)90115-7

Cited by 37 publications

(15 citation statements)

References 18 publications

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“…[102][103][104] Ethnicities and the associated different dietary and cultural habits can affect congenital anomaly rates. 105 The large animal studies of the 1980s and 1990s demonstrated that damage could be transmitted through the father to both the first [42][43][44][46][47][48][49] and second generation. 50 It was originally assumed that this transmission was limited to genetically-based inheritance.…”

Section: Discussionmentioning

confidence: 99%

“…By using this type of study design, we have examined the following compounds using chronic and acute exposure: cyclophosphamide, 1,3-butadiene and urethane (ethyl carbamate) ( Table 1). [42][43][44][45][46][47][48][49] Cyclophosphamide was positive for all endpoints in the rat after chronic gavage exposure. 43,44 This effect has also been shown by others 45 and led to the belief that chronic exposure might be a more realistic model than acute exposure, as man is chronically exposed in the workplace and environmentally.…”

Section: Paternal Exposure To Chemicalsmentioning

confidence: 99%

“…They can be measured and scored in the same way as teratogenic defects after in utero exposure of females. [42][43][44][46][47][48][49] A1b: If delayed effects in the offspring are considered as childhood cancers, cognitive developmental defects, growth disorders and the like, then in humans after radiation it was thought that exposed fathers had given rise to leukemia in their children. 63,64 However, the case was thrown out of court because it foundered on 'the balance of probabilities' .…”

Section: Questions From the Panel Q1mentioning

confidence: 99%

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Male-mediated developmental toxicity

Anderson

2005

Toxicology and Applied Pharmacology

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Section: Discussionmentioning

confidence: 99%

Section: Paternal Exposure To Chemicalsmentioning

confidence: 99%

Section: Questions From the Panel Q1mentioning

confidence: 99%

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Male-mediated developmental toxicity

Anderson

2005

Toxicology and Applied Pharmacology

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“…The Nomura studies were extensive, assaying dominant, lethal mutations, congenital malformations and, of immediate relevance, tumours among the progeny of the irradiated male or female mice of several different strains . The evidence on congenital malformations was itself novel, but has since been verified in a number of laboratories with X-rays and chemical mutagens (Kirk and Lyon 1982, 1984, Trasler et al 1985, Lyon and Renshaw 1986, Jenkinson et al 1987, Nagao 1987, 1988 . The tumour work, however, has not been repeated and, in view of its importance for the Gardner report, we have considered it essential that this be done .…”

Section: Introductionmentioning

confidence: 97%

Investigation of Lung Tumour Induction in BALB/cJ Mice Following Paternal X-irradiation

Cattanach

Patrick

Papworth

et al. 1995

International Journal of Radiation Biology

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Evidence of an enhanced incidence of lung tumours (benign adenomas and adenocarcinomas) was sought in the BALB/cJ mouse following paternal germ cell X-irradiation. In a series of replicate studies spanning approximately 1 year, males were exposed to single, acute X-ray doses of 0, 250 and 500 cGy. In each of the 2 consecutive weeks immediately thereafter they were placed with two females to generate progeny that were derived from irradiated post-meiotic cells (spermatozoa to late spermatids). These animals were then examined at 8 or 12 months for lung tumours. While the proportion of fertile females and mean litter size was affected by the radiation, showing a dose-dependent, dominant lethal response, and while cases of mutant offspring were detected, the paternal radiation did not affect lung tumour incidence in the offspring. The incidence did not vary significantly between germ cell stages irradiated (week of mating), sex of offspring, or radiation dose. However, significant differences between lung tumour incidence (mostly representing benign adenomas) were found between different replicates, these being high at the start of the study, declining and then rising to yet higher levels at its close. The finding that lung tumour incidence in BALB/cJ mice is not affected by paternal germ cell irradiation does not accord with Nomura's reports using other strains of mice. This, in turn, weakens biological support for a causal association between the raised incidence of childhood leukaemia and non-Hodgkin lymphoma near Sellafield and the father's recorded radiation exposure during employment by the nuclear industry.

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“…Among these changes, smoking in men, for example, is is reported as related to the development of tumors in their children (Sorahan et al , 1997a,b; Ji et al , 1997; Sorahan et al , 2001; Pang et al , 2003; Cordier et al , 2004; Anderson, 2005). In addition, experiments indicate that the abuse of alcohol, administration of cyclophosphamide and sodium arsenite may also relate to changes in the offspring of parents where the males were exposed to the above xenobiotics (Jenkinson et al , 1987; Jenkinson and Anderson, 1990; Oliveira et al , 2005). …”

Section: Introductionmentioning

confidence: 99%

Effects of β-glucan polysaccharide revealed by the dominant lethal assay and micronucleus assays, and reproductive performance of male mice exposed to cyclophosphamide

et al. 2014

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β-glucan is a well-known polysaccharide for its chemopreventive effect. This study aimed to evaluate the chemopreventive ability of β-glucan in somatic and germ cells through the dominant lethal and micronucleus assays, and its influence on the reproductive performance of male mice exposed to cyclophosphamide. The results indicate that β-glucan is capable of preventing changes in DNA in both germ cells and somatic ones. Changes in germ cells were evaluated by the dominant lethal assay and showed damage reduction percentages of 46.46% and 43.79% for the doses of 100 and 150 mg/kg. For the somatic changes, evaluated by micronucleus assay in peripheral blood cells in the first week of treatment, damage reduction percentages from 80.63–116.32% were found. In the fifth and sixth weeks, the percentage ranged from 10.20–52.54% and −0.95–62.35%, respectively. Besides the chemopreventive efficiency it appears that the β-glucan, when combined with cyclophosphamide, is able to improve the reproductive performance of males verified by the significant reduction in rates of post-implantation losses and reabsorption in the mating of nulliparous females with males treated with cyclophosphamide.

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Increased incidence of abnormal foetuses in the offspring of cyclophosphamide-treated male mice

Cited by 37 publications

References 18 publications

Male-mediated developmental toxicity

Male-mediated developmental toxicity

Investigation of Lung Tumour Induction in BALB/cJ Mice Following Paternal X-irradiation

Effects of β-glucan polysaccharide revealed by the dominant lethal assay and micronucleus assays, and reproductive performance of male mice exposed to cyclophosphamide

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