6-Mercaptopurine, an inducer of cytogenetic and dominant-lethal effects in premeiotic and early meiotic germ cells of male mice

Generoso, W.M.; Preston, R. Julian; Brewen, J.G.

doi:10.1016/0027-5107(75)90237-7

Cited by 62 publications

(12 citation statements)

References 14 publications

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“…The immunomodulators, azathioprine (AZA) and its active metabolite 6-mercaptopurine (6-MP), have been used since 1960 as cytostatic agents for the treatment of acute lymphoblastic leukaemia and since the 1970s to treat UC and Crohn's disease (CD). We know that AZA/6-MP are embryotoxic and teratogenic when given to pregnant female mice and rabbits at high doses,1–3 and we also know that AZA/6-MP cause chromosomal abnormalities in the sperm of male mice 4 5. Although there have been a number of studies on the birth outcomes of children delivered by mothers who took AZA/6-MP during conception and pregnancy,6–15 there is little data on the effect of AZA/6-MP on human sperm and the possible effect on the birth outcomes of children whose fathers took AZA/6-MP at the time of conception 16.…”

Section: Introductionmentioning

confidence: 99%

Reassuring results on birth outcomes in children fathered by men treated with azathioprine/6-mercaptopurine within 3 months before conception: a nationwide cohort study

Nørgård

Magnussen

Larsen

et al. 2016

Gut

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Section: Introductionmentioning

confidence: 99%

Reassuring results on birth outcomes in children fathered by men treated with azathioprine/6-mercaptopurine within 3 months before conception: a nationwide cohort study

Nørgård

Magnussen

Larsen

et al. 2016

Gut

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“…Although small in size, the study is timely given that when Zeiger [I9941 noted that "old habits and protocols die hard," he was referring to the dominant lethal assay, a primary calibrant of the present study. by Generoso et al [1975]. The format for presentation of the data is as described by Ashby and Clapp [1995].…”

Section: Corpus Epididymismentioning

confidence: 99%

Transgenic germ cell mutation assays: A small collaborative study

Ashby

1995

Environ and Mol Mutagen

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“…B spermatogonia, primary spermatocytes, the meiotic divisions, and early spermatid stages have similar morphology in all mammals. The concept of a spermatogenic wave progressing along the tubule was proposed early in the study of the testis (4,18,84), but irregularities such as reversal of the progression of stages makes it more practical to think of the succession of stages in the dimensic of time, i.e., a given spot in the tubule will pass through all stages in the cycle of the seminiferous epithelium during a time interval which is a constant for the species. This is ~207 hours in the mouse, 13 days in the rat (depending upon strain) and 16 days in man.…”

Section: Normal Gametogenesis: Malementioning

confidence: 99%

Dominant-Lethal Mutations and Heritable Translocations in Mice

Generoso

1984

Mutation, Cancer, and Malformation

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By acceptance of t h i s a r t i c l e , t h e publisher o r r e c i p i e n t acknowledges t h e U.S. Government's r i g h t t o r e t a i n a nonexclusive, r o y a l t y -f r e e l i c e n s e i n and t o any copyright covering tke a r t i c l e . U.S. Department of Energy under c o n t r a c t W-7405-eng-26 w i t h t h e UnionCarbide Corporation. SUMMARYThe primordial germ cells originate in the regloti of the caudal end of the primitive streak, root of the allantois, and yolk sac splanchuopleure, and migrate to the gonadal ridges where they divide to form the oogonia of the female and gonocytes of the male. In the female, the transition to oocytes occurs in utero, and the female mammal is born with a finite number of oocytes that cannot be replaced. By contrast, the gonocytes of the male initiate divisions soon after birth to form the spermatogonial stem cells, which persist throughout reproductive life of the male and are capable of regenerating the seminiferous epithelium after injury. As a result of these basic differences in gametogenesis, the response of the male and female to radiation and chemicals is different. Any loss of oocytes in the female cannot be replaced, and if severe enough, will result in a shortening of the reproductive span. In the male, a temporary sterile period may be induced owing to destruction of the differentiating spermatogonia, but the stem cells are the most resistant spermatogonial type, are capable of repopulating the seminiferous epithelium, and fertility usually returns. The response of both the male and female changes with development of the embryonic to the adult gonad, and with differentiation and maturation in the adult. The primordial germ cells, early oocytes, and differentiating spermatogonia of the adult male are unusually sensitive to the cytotoxic action of noxious agents, but each agent elicits a specific response owing to the intricate biochemical and physiological changes associated with development and maturation of the gametes. The relationship of germ cell killing to fertility is direct, and long-term fertility effects can be predicted from histological analysis of the gonads. The relationship to genetic effects on the other hand, is indirect, and acts primarily by limiting the cell stages available for testing, by affecting the distribution of mitotically active stem cells among the different stages of the mitotic cycle, and thereby, changing both the type and frequency of genetic effects observed. INTRODUCTIONThe level of our understanding of the effect of radiation, chemicals, pollutants, and noxious agents in general on the gonads, and the relationship of these effects to fertility and to transmission of genetic damage is dependent upon our understanding of the normal process of germ cell development. Some of the problems to be discussed here were phrased over a century ago, but it is only within the last thirty years that the direct lineage between primordial germ cells and the definitive gametes has been firmly established, and significant progress i...

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6-Mercaptopurine, an inducer of cytogenetic and dominant-lethal effects in premeiotic and early meiotic germ cells of male mice

Cited by 62 publications

References 14 publications

Reassuring results on birth outcomes in children fathered by men treated with azathioprine/6-mercaptopurine within 3 months before conception: a nationwide cohort study

Reassuring results on birth outcomes in children fathered by men treated with azathioprine/6-mercaptopurine within 3 months before conception: a nationwide cohort study

Transgenic germ cell mutation assays: A small collaborative study

Dominant-Lethal Mutations and Heritable Translocations in Mice

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