Neutron radiation, a high-linear energy transfer radiation, has a high relative biological effectiveness (RBE) for various end points. The age at exposure is an important modifier of the effects of radiation, including carcinogenesis, with infants being generally more radiosensitive. Ptch1^+/– mice offer a unique experimental system for assessing radiation carcinogenesis. Spontaneous development of medulloblastoma tumors occurs in nonirradiated animals that lose their Ptch1⁺ allele, most frequently by a loss of heterozygosity (LOH) of chromosome 13 via recombination or non-disjunction (referred to as S-type tumors). In contrast, tumors occur in irradiated Ptch1^+/– mice as a result of chromosome 13 LOH with an interstitial deletion (R-type), making spontaneous and radiation-induced tumors discernible. To elucidate the influence of age on the effect of fast neutrons, we irradiated Ptch1^+/– mice with neutrons (mean energy, ∼2 MeV) or γ rays on embryonic day (E)14 and E17 and on postnatal day (P)1, 4 or 10 and classified the resulting medulloblastomas based on chromosome 13 aberrations. Instead of LOH, some tumors harbored mutations in their Ptch1⁺ gene via a nonirradiation-associated mechanism such as duplication, insertion, base substitution or deletion with microhomology-mediated end joining; thus, these tumors were classified as S-type. The RBE regarding the induction of R-type tumors was 12.9 (8.6, 17.2), 9.6 (6.9, 12.3), 21.5 (17.2, 25.8), and 7.1 (4.7, 9.5) (mean and 95% confidence interval) for mice irradiated on E14, E17, P1 and P4, respectively, with the highest value seen during the most active development of the tissue and P10 being completely resistant. These results indicate that the developmental stage at exposure of the tissue influences the RBE of neutrons.

中子辐射是一种高线性能量转移辐射，对各种终点具有较高的相对生物有效性 (RBE)。暴露年龄是辐射影响的重要调节因素，包括致癌作用，婴儿通常对辐射更敏感。Ptch1 ^+/–小鼠提供了一个独特的实验系统来评估辐射致癌作用。髓母细胞瘤肿瘤的自发发生在失去Ptch1 ⁺等位基因的未受辐射动物中，最常见的原因是 13 号染色体通过重组或不分离（称为 S 型肿瘤）的杂合性 (LOH) 丢失。相反，肿瘤发生在受照射的Ptch1 ^+/–小鼠由于 13 号染色体 LOH 具有间质缺失（R 型），使得自发性和辐射诱导的肿瘤可辨别。为了阐明年龄对快中子效应的影响，我们在胚胎日 (E)14 和 E17 以及出生后日 (P)1 用中子（平均能量，~2 MeV）或 γ 射线照射Ptch1 ^+/–小鼠、 4 或 10 并根据染色体 13 畸变对由此产生的髓母细胞瘤进行分类。而不是 LOH，一些肿瘤在其Ptch1 ⁺基因通过非辐射相关机制，如复制、插入、碱基替换或缺失，微同源介导的末端连接；因此，这些肿瘤被归类为S型。对于受照射的小鼠，关于诱导 R 型肿瘤的 RBE 为 12.9 (8.6, 17.2)、9.6 (6.9, 12.3)、21.5 (17.2, 25.8) 和 7.1 (4.7, 9.5)（平均值和 95% 置信区间）分别在 E14、E17、P1 和 P4 上，在组织最活跃发育期间看到的最高值和 P10 完全耐药。这些结果表明，组织暴露时的发育阶段会影响中子的 RBE。