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Influence of hormonal disturbances on transplacental and multigeneration carcinogenesis in rats
V A Alexandrov1, I G Popovich, V N Anisimov
1N.N. Petrov Research Institute of Oncology, Leningrad, USSR.
Abstract:
Thyroid dysfunction (induced by thyroidectomy or administration of thyroxin and methylthiouracil) during the postnatal period was tested as a modifying factor on carcinogenesis induced transplacentally by N-methyl-N-nitrosourea (MNU). It resulted mainly in inhibition of tumours of the nervous system and kidney in rats of two subsequent generations, but thyroid carcinogenesis was increased. Postnatal disturbance of oestrous function (induction of persistent oestrus syndrome) in female rats increased the incidence of tumours of the central nervous system induced transplacentally by MNU or 7,12-dimethylbenz[a]anthracene. No such effect was seen in animals of the F2 generation.
Insights
Postnatal thyroid dysfunction inhibited nervous system and kidney tumors but increased thyroid tumors in rats. Disturbing oestrous cycles also increased central nervous system tumors, showing lasting effects on carcinogenesis.
Area of Science:
- Endocrinology
- Toxicology
- Developmental Biology
Background:
- Carcinogenesis can be influenced by various factors, including hormonal status and developmental stage.
- The impact of postnatal endocrine disruption on transplacental carcinogenesis is not fully understood.
Purpose of the Study:
- To investigate the modifying effects of postnatal thyroid dysfunction on transplacental carcinogenesis.
- To examine the influence of induced persistent oestrus on tumor development following transplacental carcinogen exposure.
Main Methods:
- Thyroid dysfunction was induced in rats postnatally via thyroidectomy, thyroxin, or methylthiouracil administration.
- Persistent oestrus syndrome was induced in female rats.
- Carcinogenesis was initiated transplacentally using N-methyl-N-nitrosourea (MNU) or 7,12-dimethylbenz[a]anthracene (DMBA).
Main Results:
- Postnatal thyroid dysfunction primarily inhibited nervous system and kidney tumors in two subsequent rat generations.
- Thyroid carcinogenesis was significantly increased following postnatal thyroid dysfunction.
- Disturbance of oestrous function elevated the incidence of central nervous system tumors induced by MNU or DMBA, with no effect in the F2 generation.
Conclusions:
- Postnatal thyroid dysfunction acts as a modifier of transplacental carcinogenesis, with differential effects on various tumor types.
- Disruption of the oestrous cycle in early life can enhance susceptibility to specific carcinogen-induced tumors.
- These findings highlight the critical role of endocrine status during development in modulating cancer risk.