Influence of irradiation and chemotherapy on the ovaries of children with abdominal tumours

Himelstein-Braw, Ruth; Peters, Hannah; Faber, Mogens

doi:10.1038/bjc.1977.186

Cited by 82 publications

(28 citation statements)

References 15 publications

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“…In the present study, it varied between 4 and 5 yr. However, up to 7 yr after irradiation, a normal gonadotropin response to radiation-induced ovarian atrophy could also be observed (21). This indicates great individual variations and the necessity for a complete work up in cases with abnormal puberty.…”

Section: Discussionmentioning

confidence: 99%

Effect of Hypothalamic and Pituitary Irradiation on Pubertal Development in Children with Cranial Tumors

Rappaport

Brauner

Czernichow

et al. 1982

The Journal of Clinical Endocrinology & Metabolism

153

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The purpose of the present study was to report on gonadotropin function and puberty of a large group of children treated by cranial irradiation for cranial and neck tumors and medulloblastoma. Forty-five children of pubertal age were investigated. The mean interval time since radiation was 5 2/12 yr. Gonadotropin and gonadal function were evaluated by clinical criteria, plasma sex steroids, and plasma LH and FSH responses to LRH. Puberty was complete or progressing normally in 31 cases and was abnormal in 14 cases. Severe gonadotropin deficiency, with lack of or slow progression of puberty and decreased LH and FSH responsiveness to LRH, was observed in 5 cases; 2 of these had moderately elevated plasma PRL levels. Secondary amenorrhea or lack of pubertal progression was found in 5 other cases. GH deficiency was associated with gonadotropin deficiency in 9 of these 10 cases. Adrenal function, estimated by basal dehydroisoepiandrosterone, dehydroisoepiandrosterone sulfate, and estrone, was normal according to pubic hair stages. In conclusion, complete or partial gonadotropin deficiency can be the consequence of cranial irradiation in children receiving 6000 rads or less. It is usually associated with GH deficiency. The site of the damage on the pituitary gland or the hypothalamus remains to be demonstrated.

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Section: Discussionmentioning

confidence: 99%

Effect of Hypothalamic and Pituitary Irradiation on Pubertal Development in Children with Cranial Tumors

Rappaport

Brauner

Czernichow

et al. 1982

The Journal of Clinical Endocrinology & Metabolism

153

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“…Ovarian follicles are remarkably vulnerable to agents that cause DNA damage such as ionizing radiation and chemotherapeutic drugs 33 . Primordial follicles in mouse ovaries are among the most radiosensitive of all mammalian cells and have an LD 50 of only ~ 0.5 Gy.…”

Section: Cytotoxic Damagementioning

confidence: 99%

Programmed cell death in the reproductive system

Gosden

Spears

1997

British Medical Bulletin

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The reproductive system presents some of the best examples of programmed cell death, which is to be expected considering the dramatic cycles of tissue growth and regression in females. Hormones from the pituitary gland, gonads and uterus are responsible for coordinating cycles in which the preservation of cell survival and inhibition of apoptosis are important. In the ovary, atresia regulates the size of the follicle cohort forovulation and is an archetype of apoptosis as induced by hormone withdrawal.The fate of an antral follicle -growth or atresia -is determined by circulating levels of gonadotrophins, and follicle-stimulating hormone (FSH) in particular. At the end of a menstrual cycle or pregnancy or lactation, hormone withdrawal triggers cell death and tissue remodelling and initiates a fresh cycle. In the endometrium, breast and prostate gland, steroid hormones are the principal survival factors and castration triggers regression of responsive tissues, which is sometimes decisive in the fight against disease. But while the primary trigger of cell death varies between tissues, underlying cellular mechanisms are more conservative and cell death/ survival genes, such as bcl-2, bax and others that are expressed in other tissues, play important roles in the reproductive system too. Apoptosis or programmed cell death is more obvious and has been more intensively investigated in the reproductive organs than in almost any other system. Indeed, dying cells were described in the Graafian follicles of rabbit ovaries as long ago as 1885, although the phenomenon was then called 'chromatolysis' rather than apoptosis. One explanation for cell death in the reproductive system is that it is required because of the cyclical growth and re-modelling of tissues occurring throughout adult life -at least until menopause in females. Another reason is that far more germ cells are produced than are needed. The gonads are not the only organs generating excess cells, though they are unusual insofar as the wastage continues on a large scale in adult life. In the endometrium, epithelial and stromal tissues grow and differentiate until the menstrual cycle is terminated by programmed regression of the functional layerunless conception occurs first. Parallel, though less obvious, changes occur in breast and other tissues, the whole process being coordinated by pituitary and ovarian hormones. Few systems, if any, provide such clear demonstrations of the pivotal role of hormones in determining cell fate.

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“…In addition, cancer treatment can reduce the ovarian follicular reserve, resulting in premature ovarian failure (POF) (Hudson, 2010). Fewer primordial follicles have been demonstrated in autopsied ovarian samples (Himelstein-Braw et al, 1977) and fewer antral follicles detected by ultrasound (Larsen et al, 2003) in females that received anti-neoplastic treatment compared to their age-matched control subjects.…”

Section: Introductionmentioning

confidence: 99%

Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells

Ganesan

Keating

2015

Toxicology and Applied Pharmacology

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Phosphoramide mustard (PM), the ovotoxic metabolite of the anti-cancer agent cyclophosphamide (CPA), destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage. A previous study demonstrated that PM induces ovarian DNA damage in rat ovaries. To investigate whether PM induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6 μM) for 24 or 48 h. Cell viability was reduced (P < 0.05) after 48 h of exposure to 3 or 6 μM PM. The NOR-G-OH DNA adduct was detected after 24 h of 6 μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48 h by exposure to both PM concentrations. Phosphorylated H2AX (γH2AX), a marker of DNA double stranded break occurrence, was also increased by PM exposure, coincident with DNA adduct formation. Additionally, induction of genes (Atm, Parp1, Prkdc, Xrcc6, and Brca1) and proteins (ATM, γH2AX, PARP-1, PRKDC, XRCC6, and BRCA1) involved in DNA repair were observed in both a time- and dose-dependent manner. These data support that PM induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response.

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Influence of irradiation and chemotherapy on the ovaries of children with abdominal tumours

Cited by 82 publications

References 15 publications

Effect of Hypothalamic and Pituitary Irradiation on Pubertal Development in Children with Cranial Tumors

Effect of Hypothalamic and Pituitary Irradiation on Pubertal Development in Children with Cranial Tumors

Programmed cell death in the reproductive system

Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells

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