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

## TL;DR

Apigenin, a natural compound, may help prevent radiation-induced cancer in mice by reducing inflammation and supporting gut health.

## Contribution

Apigenin is shown to reduce the risk of acute lymphoma/lymphoblastic leukemia in mice exposed to space-like radiation.

## Key findings

- Mice not fed apigenin had a 2.25 times higher cancer risk compared to those fed apigenin.
- Apigenin improved survival rates, with 63% survival in apigenin-fed mice versus 37% in non-fed mice.
- Apigenin may protect by reducing inflammation and maintaining gut microbiome health.

## Abstract

Cancer induction from space radiation poses a significant health risk for astronauts, necessitating effective protective measures. Current shielding is inadequate, highlighting the need for novel biological countermeasures. One promising candidate is apigenin (AP), a natural compound known for its antioxidant and anti-inflammatory effects. This study focuses on how AP might help protect mice from developing acute lymphoma/lymphoblastic leukemia after being exposed to silicon ions (28Si). The results showed that mice not fed an AP diet had a 2.25 times higher chance of developing cancer compared to those that did eat AP. This suggests that AP could help prevent cancer caused by radiation. We believe that AP works by reducing inflammation caused by radiation in both the bone marrow and the gut, and it may also help keep the gut bacteria healthy. We also propose that the connection between the gut microbiome and the bone marrow (called the gut–bone marrow axis) plays a role in how the immune system responds to 28Si and impacts the development of these cancers.

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.