Interpretation of the increase in the frequency of neoplastic transformations observed for some ionising radiations at low dose rates.

The anomalous increase of transformation frequency with decreasing dose rate observed by Hill et al. (1982, 1984b) for mouse fibroblast cells irradiated with fission neutrons cannot be satisfactorily explained by current models of radiation action. Recently a new model has been proposed which predicts the enhancement of damage with prolongation of irradiation, for equal doses. This is applied to the transformation studies in an attempt to interpret the enhancement observed for some radiations but not for others. Evidence is presented which suggests that repaired double-strand breaks in the DNA of cells which survive are the precursors of transformation. A critical physical factor is the total irradiation time rather than the dose rate. Approximately 1 per cent of repaired surviving cells go on to transform. From the results an explanation emerges of why transformation enhancement at low dose rates is not observed for natural alpha radiation and for photons or electrons, but is observed for fission neutrons and fast iron ions.

Brain serotonin determines maternal behavior and offspring survival.

Maternal care is an indispensable component of offspring survival and development in all mammals and necessary for reproductive success. Although brain areas regulating maternal behaviors are innervated by serotonergic afferents, very little is known about the role of this neurotransmitter in these behaviors. To evaluate the contribution of serotonin to maternal care, we used mice with a null mutation in the gene for tryptophan hydroxylase-2 (TPH2), which results in a genetic depletion of brain serotonin, and tested them in a wide range of maternal behavior paradigms. We found that litters born to and reared by TPH2(-/-) mothers showed decreased survival, lower weaning weights and increased cannibalization. In addition, TPH2(-/-) mothers performed poorly in pup retrieval, huddling, nest construction and high-arched back nursing. Aggression in TPH2(-/-) dams was not triggered by lactation and was steadily high. Survival and weaning weight deficits of TPH2(-/-) pups were rescued by cross-fostering and in litters of mixed genotype (TPH2(-/-) and TPH2(-/+) ). However, the maternal behaviors of TPH2(-/-) dams did not improve when rearing either TPH2(+/+) pups or mixed-genotype litters. In addition, TPH2(-/-) pups significantly worsened the behavior of TPH2(+/+) dams with respect to cannibalism, weaning weight and latency to attack. Olfactory and auditory functions of TPH2(-/-) females or anxiety-like behaviors did not account for these maternal alterations as they were equal to their TPH2(+/+) counterparts. These findings illustrate a profound influence of brain serotonin on virtually all elements of maternal behavior and establish that TPH2(-/-) pups can engender maladaptive mothering in dams of both genotypes.