Daily Consumption of Apigenin Prevents Acute Lymphoma/Lymphoblastic Leukemia in Male C57BL/6J Mice Exposed to Space-like Radiation

Abstract

Introduction: The work presented here is part of our study series aimed at investigating the countermeasure effectiveness of apigenin (AP) against both early and late effects of heavy silicon (²⁸Si) on the same cohort of exposed male C57BL/6 mice. We previously reported the countermeasure of AP against ²⁸Si-induced early effects of ²⁸Si ions. This section focuses on the protective effects of AP on late effects, specifically on the induction of acute lymphoma/lymphoblastic leukemia.

Method: Mice received a diet containing 20 mg/kg body weight of AP for five days before and after total-body irradiation with either 0 or 0.5 Gy of 260 MeV ²⁸Si ions. They were divided into four groups based on AP intake and irradiation status. At one-week after irradiation, six mice from each group were euthanized to assess AP's effectiveness against early inflammation (in the bone marrow and gut tissues) and gut dysbiosis. The remaining mice were monitored until approximately 770 days of age. Incidence rates were analyzed using Chi-Square tests, while survival data were evaluated with Kaplan-Meier plots and log-rank tests, setting significance at p ≤ 0.05.

Results: At 770 days, survival rates were 37% for ²⁸Si-exposed mice and 63% for those consuming AP, despite irradiation. There was a 2.57-fold increase in acute lymphoma/lymphoblastic leukemia incidence among ²⁸Si-exposed mice not receiving AP compared to controls and AP-fed mice. Together with our previous report on the countermeasure activity of AP against early effects, these findings suggest that the gut-bone marrow axis plays an important role in ²⁸Si-induced acute lymphoma/lymphoblastic leukemia.

Conclusion: Our findings demonstrate that AP is an effective means of tackling the challenges posed by space radiation, and it has the potential to revolutionize protection in this critical area.

Keywords: apigenin; chemoprevention; lymphoblastic leukemia; mitigation; protection; space radiation.

Figure 1

Chemical structure of apigenin.

Figure 2

Experimental design.

Figure 3

Temporal changes in the mean weight.

Figure 4

Survival curve of each group.

Figure 5

Incidence of acute lymphoma/lymphoblastic leukemia (LL).

Figure 6

Histopathological evidence of infiltration by acute lymphoma/lymphoblastic leukemia cells into various organs ((A), (B), (C) by H&E staining in the spleen, the liver, and the lung, respectively; while (D) is an example of CD45 positive IHC results in the infiltrated lung tissue of an acute lymphoma/lymphoblastic case).