We have tested an 836.55 MHz field with North American Digital Cellular (NADC) modulation in a 2-year animal bioassay that included fetal exposure. In offspring of pregnant Fischer 344 rats, we tested both spontaneous tumorigenicity and the incidence of induced central nervous system (CNS) tumors after a single dose of the carcinogen ethylnitrosourea (ENU) in utero, followed by intermittent digital-phone field exposure for 24 months. Far-field exposures began on gestational day 19 and continued until weaning at age 21 days. Near-field exposures began at 35 days and continued for the next 22 months, 4 consecutive days weekly, 2 h/day. SAR levels simulated localized peak brain exposures of a cell phone user. Of the 236 original rats, 182 (77%) survived to the termination of the whole experiment and were sacrificed at age 709-712 days. The 54 rats (23%) that died during the study ("preterm rats") formed a separate group for some statistical analyses. There was no evidence of tumorigenic effects in the CNS from exposure to the TDMA field. However, some evidence of tumor-inhibiting effects of TDMA exposure was apparent. Overall, the TDMA field-exposed animals exhibited trends toward a reduced incidence of spontaneous CNS tumors (P < 0. 16, two-tailed) and ENU-induced CNS tumors (P < 0.16, two-tailed). In preterm rats, where primary neural tumors were determined to be the cause of death, fields decreased the incidence of ENU-induced tumors (P < 0.03, two-tailed). We discuss a possible approach to evaluating with greater certainty the possible inhibitory effects of TDMA-field exposure on tumorigenesis in the CNS.

In response to acute maternal hypoxia, ornithine decarboxylase (ODC) activity increased significantly in fetal rat brain, peaking at 4 h. This was associated with increased ODC mRNA and elevated polyamine concentrations. To correlate this response with development, we measured ODC activity in the rat from gestational day E 17 to postnatal day P 10. We also examined to what extent hypoxia induces increased ODC activity in adult rat brains and whether the response to chronic hypoxia differed from that to acute hypoxia. To test the hypothesis that this increased activity is due to hypoxic hypoxia per se, we subjected pregnant dams to inspired carbon monoxide concentrations ranging from 150 to 1000 ppm and assayed ODC activity in the fetal brain 4 h later. In the fetus, ODC activity was elevated on E 17 in the cerebrum and cerebellum. It declined gradually to about one-tenth E 17 levels by E 21 and remained low thereafter except for a postnatal elevation in the cerebellum on P 3. In response to 10.5% O2, in the 3-day-old rat, ODC activity peaked between 2 and 3 h of hypoxia, increasing 3-fold in the hippocampus and 2-fold in cerebellum. Similar increases were seen in the hypoxic adult rat brain. In inspired oxygen dose-response studies, exposure of P 3 rat pups to 13.25% O2 for 2.5 h produced a 1.5-fold increase in ODC activity; 10.5% O2 produced a 2-3-fold increase while in response to 9% O2, ODC activity remained at baseline levels. With maternal CO-hypoxia, ODC activity increased in the fetal brain at 4 h, as seen with hypoxic-hypoxia. For example, in hippocampus, ODC activity doubled at 500 ppm and tripled at 600 ppm. We conclude: (1) apparently, the ability to respond thus is not lost as the animal ages and may represent an important cellular response to acute hypoxia; (2) the increase in hypoxic-induced ODC activity is relative to the already elevated activity seen from E 17 to E 20; a vast reserve for the induction of fetal ODC activity probably exists and may indicate the importance of this enzyme during this time frame for differentiation and growth promotion; and (3) the CO-hypoxia studies suggest that some aspects of the cellular responses to CO- and hypoxic-hypoxia are similar.

Several studies have examined behavioral sequelae of acute or chronic pre- or postnatal hypoxia. However, few of these tested a large battery of behavioral functions, particularly those following relatively mild, intermittent hypoxia. Also, in few studies were the hypoxic pups cross-fostered or the experimenter blinded as to experimental group. In addition, in almost no studies were concomitant hypoxic-induced brain biochemicals measured. The present study tested the hypotheses that mild, intermittent antenatal hypoxia can lead to long-term alterations in neurobehavioral development, as well as neurochemical changes.