Current Evidence for Developmental, Structural, and Functional Brain Defects following Prenatal Radiation Exposure

Table 1

DNA damage, repair mechanisms, and cell death in the irradiated prenatal neocortex of rodents.

Stage	Time after irradiation	Dose	Effect	References
			DNA damage and repair
E13.5	1 h	0.01–0.1 Gy	Dose-dependent DNA damage	[33]
	6 h	0.1 Gy	Strong reduction in DNA damage foci, not observed at lower doses (0.01–0.05 Gy)	[33]
E14.5	1 h	0.1–0.5 Gy	Dose-dependent and widespread DNA damage, average of 2-3 foci/cell	[36, 37]
			NHEJ in VZ/SVZ; 0.1 Gy: partial G2/M cell cycle arrest, 4–6 DSBs in G2 cells; 0.5 Gy: full G2/M arrest	[36]
		2.0 Gy	Widespread DNA damage	[31]
	4 h	2.0 Gy	G2/M checkpoint release/restart of mitosis	[38]
	6 h	0.5 Gy	G2/M checkpoint release with 67% of mitotic cells having remaining DSB foci	[36]
	24 h	2.0 Gy	Full DNA damage repair, which occurred slower in VZ/SVZ progenitors	[31]
			Apoptosis
E11	24 h	1.0 Gy	Apoptosis mainly restricted to CP	[39]
E12.5	4 h	14 Gy	Widespread apoptosis, ATM-independent	[40]
E12–E13	6 h	1.0 Gy	50% decrease in viable cells, caspase-9 dependent	[41]
E13-E13.5	6 h	0.01–0.2 Gy	Increased apoptosis mainly restricted to VZ/SVZ	[33]
		1.5–3 Gy	Dose-dependent, widespread apoptosis	[42]
E14.5	4–8 h	1.0–2.0 Gy	Dose-dependent increase in apoptosis, gradual from VZ (high) to IZ (low); Rad54 (HR)-dependent cell survival in S- and G2-phase irradiated cells	[38, 43]
	3-4 h	2.0 Gy	High radiosensitivity of G2/M phase cells, p21-independent; Proapoptotic effect of p21 on IZ cells; Cells irradiated in S-phase enter intra-S checkpoints, leading to delayed INM and apoptosis	[38]
	6 h	0.05–0.1 Gy	Moderate apoptosis mainly in VZ/SVZ	[36]
		0.5 Gy	>1% apoptosis, mainly in VZ/SVZ; 75% ATM-dependent in VZ/SVZ, 15% ATM-dependent in IZ/CP	[36]
	14 h	≥0.1 Gy	Reduced apoptosis in VZ/SVZ; Apoptosis in IZ resulting from persisting DSBs	[36]
	24 h	2.0 Gy	Peak of apoptosis still in VZ/SVZ, but increased apoptosis in CP	[31]
			Peak of apoptosis in the IZ	[44]
E15-E15.5	3 h	0.5 Gy	60% apoptosis in SVZ, 25% in IZ + CP	[45]
	4 h	14 Gy	Widespread apoptosis, ATM dependency only in SVZ	[40]
	24 h	0.5 Gy	Gradual increase in upper layer apoptosis; 70% apoptosis in IZ + CP	[45]
E17	4 h + 24 h	0.1–0.2 Gy	Apoptosis in VZ/SVZ + IZ, no difference in PI time points	[46]
		0.4 Gy	Apoptosis in VZ/SVZ + IZ + CP, no difference in PI time points	[46]

E = embryonic stage, Gy = gray, NHEJ = nonhomologous end-joining, HR = homologous recombination, DSB = double-strand break, VZ = ventricular zone, SVZ = subventricular zone, IZ = intermediate zone, CP = cortical plate, ATM = ataxia telangiectasia mutated, and INM = interkinetic nuclear migration.