TABLE 3.

Studies reporting the combined effects of space environment in human cells.

Studied materials	Experimental treatments	Combined biological effects	Refs
Human peripheral blood lymphocytes	γ-rays (0.2, 2 Gy) + RWV (4, 24 h)	Decreased number of radio-responsive miRNAs	Girardi et al. (2012)
Human lymphocytes	X-rays/protons (1–6 Gy) + RWV (24 h)	No effect on CA	Manti et al. (2005)
Human fibroblast 1BR-hTERT cells	X-rays/carbon ions (0.5, 1.5 Gy)-3D clinostat (24 h)	Increased CA	Hada et al. (2019)
Human lymphoblastic TK6 cells	X-rays/carbon ions (0.5, 1.5 Gy)-3D clinostat (24 h)	Increased CA	Yamanouchi et al. (2020)
Human lymphocytes	X-rays (1.5 Gy) + cuvette clinostat (2 h)	Increased CA	Mosesso et al. (2001)
Human peripheral blood lymphocytes	γ-rays (5 Gy) + RWV (0.5, 2, 6, 24 h)	Decreased DNA damage repair	Mognato et al. (2009)
Human skin fibroblast NHF-23 cells	X-rays (5, 10 Gy) + real microgravity (4.5 h)	No effect on DNA damage repair	Horneck et al. (1996)
Human lymphoblastoid TK6 cells	γ-rays (1, 2, 4 Gy) + RWV (24 h)	Decreased apoptosis	Canova et al. (2005)
Human B lymphoblastoid HMy2.CIR cells	RWV (30 min) + carbon ions (0.2, 0.4, 0.6, 0.8 Gy)	Increased cell survival and apoptosis	Dang et al. (2014)
Human peripheral blood lymphocytes	X-rays/γ-rays (1, 2 Gy) + RWV (24 h)	Increased HPRT mutation frequency	Mognato and Celotti (2005)
Human fibroblasts 1BR-hTERT cells	X-rays/carbon ions (1 Gy, 0.03 Gy/min)-3D clinostat (48 h)	DNA damage and failure of cell cycle checkpoint block	Ikeda et al. (2019)
Human lymphoblast TK6 cells	γ-rays (2 Gy) + RWV (24 h)	Additive/synergistic effects on RNA expression patterns/levels	Fu et al. (2020)
Human lung epithelial cells BEAS-2B	3D clinostat (48 h) + X-rays (2 Gy)	Increased DNA damage, apoptosis and RAC2 expression and inhibition of proliferation and survival additively	Tan et al. (2020)

“+”: sequential treatments; “-”: simultaneous treatments.