THE RELATIONSHIP BETWEEN APOPTOSIS AND ATROPHY IN THE IRRADIATED LACRIMAL GLAND

THE RELATIONSHIP BETWEEN APOPTOSIS AND ATROPHY IN THE IRRADIATED LACRIMAL GLAND
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DOI:
10.1016/0360-3016(92)90716-u
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发表时间:
1992-01-01
影响因子:
7
通讯作者:
PETERS, LJ
PETERS, LJ
中科院分区:
医学1区
文献类型:
--
作者:
GAZDA, MJ;SCHULTHEISS, TE;PETERS, LJ

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萎缩通常被认为是辐射的真正晚期效应。然而,在浆液腺中,萎缩被认为是一种间接的晚期效应,因为浆液细胞在照射后数小时内死亡,并且在放射治疗的同时观察到明显的萎缩效应。因此,为了确定浆液性腺体萎缩的发病机制,有必要区分由于浆液性细胞的直接辐射死亡导致的实质损失和由于继发于纤维化、血管损伤或前体细胞死亡的浆液性细胞死亡导致的实质损失。本文报道62只恒河猴的泪腺经2.5 ~ 20戈伊的单次照射后,每隔4小时~ 112天检查一次。在每个(剂量,时间)点至少30个高倍视野中对浆液细胞(细胞核)和腺泡进行计数。在每个剂量和处死时间,计算每个腺泡的平均细胞核数和每个高倍视野的平均腺泡数。此外,在每个剂量和时间,检查每个腺泡的细胞核数量分布,以确定腺泡大小的频率如何作为辐射的函数变化。每个腺泡的细胞数量最初似乎增加,但这可能是由于脱颗粒细胞物理上较小,产生人为的较高计数的结果。在12.5戈伊照射后4天内,每个腺泡的平均核数接近对照值,并保持在对照范围内至少112天。在12.5戈伊照射后30天内,每个高倍视野的腺泡数量稳定下降。从30天到112天,这一数字有所恢复,但仍远低于对照值。在24小时,每个腺泡的细胞核数显示出明显的剂量反应高达20戈伊。然而,在30天时,没有证据表明该参数存在剂量反应。这些结果表明,即使浆液细胞在照射后数小时内大量死亡,泪腺(以及扩展到腮腺)的萎缩也是浆液干细胞或前体细胞死亡的结果。因此,保护浆膜细胞免受辐射凋亡不会减少浆膜腺萎缩。
Atrophy is generally considered to be a true late effect of radiation. However, in serous glands, atrophy was thought to be a consequential late effect because serous cells die within hours of irradiation and the apparent effects of atrophy are observed contemporaneously with radiation treatment. Therefore, to determine the pathogenesis of atrophy in serous glands, it is necessary to differentiate between parenchymal loss as a result of direct radiation death of serous cells and parenchymal loss as a result of serous cell death that is secondary to fibrosis, vascular damage, or precursor cell death. The lacrimal glands of 62 rhesus monkeys have been irradiated to single doses of 2.5 to 20 Gy and examined at intervals of 4 hr to 112 days postirradiation. Serous cells (nuclei) and acini were counted in at least 30 high power fields per (dose, time) point. At each dose and time of sacrifice, the average number of nuclei per acinus and the average number of acini per high power field were calculated. Also at each dose and time, the distribution of the number of nuclei per acinus was examined to determine how the frequency of acinar sizes changed as a function of irradiation. The number of cells per acinus appears to rise initially, but this is likely a result of the degranulated cells being physically smaller, yielding an artificially higher count. Within 4 days after 12.5 Gy, the average number of nuclei per acinus approaches control values and remains within the range of controls for at least 112 days. The number of acini per high power field decreases steadily for 30 days after 12.5 Gy. From 30 to 112 days, there is some recovery of this number, but it remains well below control values. At 24 hr, the number of nuclei per acinus shows a distinct dose response up to 20 Gy. However, at 30 days there is no evidence of a dose response for this parameter. These results indicate that even though serous cells die in significant numbers within hours of irradiation, the atrophy of the lacrimal gland (and by extension, the parotid gland) is a result of the death of the serous stem cell or precursor. Consequently, protection of serous cells from radiation apoptosis will not diminish serous gland atrophy.