Emerging issues in radiogenic cataracts and cardiovascular disease

Abstract

In 2011, the International Commission on Radiological Protection issued a statement on tissue reactions (formerly termed non-stochastic or deterministic effects) to recommend lowering the threshold for cataracts and the occupational equivalent dose limit for the crystalline lens of the eye. Furthermore, this statement was the first to list circulatory disease (cardiovascular and cerebrovascular disease) as a health hazard of radiation exposure and to assign its threshold for the heart and brain. These changes have stimulated various discussions and may have impacts on some radiation workers, such as those in the medical sector. This paper considers emerging issues associated with cataracts and cardiovascular disease. For cataracts, topics dealt with herein include (i) the progressive nature, stochastic nature, target cells and trigger events of lens opacification, (ii) roles of lens protein denaturation, oxidative stress, calcium ions, tumor suppressors and DNA repair factors in cataractogenesis, (iii) dose rate effect, radiation weighting factor, and classification systems for cataracts, and (iv) estimation of the lens dose in clinical settings. Topics for cardiovascular disease include experimental animal models, relevant surrogate markers, latency period, target tissues, and roles of inflammation and cellular senescence. Future research needs are also discussed.

Keywords: cardiovascular disease; cataract; radiation protection; threshold.

Fig. 1.

Changes in estimates of the minimum cataractogenic dose for a 50-year exposure estimated by a Strandqvist plot. The minimum cataractogenic dose to produce human cataracts in each of three exposure conditions (a single exposure, exposure over 3 weeks to 3 months, and exposure over 3 months to 9 years) was taken from Merriam and Focht [18], and plotted on a log–log scale as a function of exposure time (i.e. a Strandqvist plot [26]). Equation of the fitted line, its correlation coefficient square (r²), and the estimated minimum cataractogenic dose in röntogen (r) for a 50-year exposure (D_50y) estimated from the fitting equation are shown in each panel (n.b. 1 r roughly corresponds to 1 cGy). The time of a single exposure was treated as 4 h according to Merriam et al. [27], and 50 years were treated as 18 262.5 days. (A) The minimum dose to produce a cataract in each exposure condition, irrespective of whether the cataract is stationary or progressive. (B) The minimum dose to produce a stationary cataract in each exposure condition. (C) The minimum dose to produce a progressive cataract in each exposure condition. Note that Merriam and Focht [18] used the term ‘cataract’ to mean all clinically recognizable opacities (i.e. both minor opacities and VICs), ‘stationary cataract’ to mean the opacity that remains stationary at any stage or progresses slowly over a considerable period and then remains stationary (i.e. a cataract that does not progress to a VIC), and ‘progressive cataract’ to mean the opacity that continues to progress to a VIC and becomes non-specific.

Fig. 2.

Redox regulation in the lens. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), and a newly characterized family of antioxidant molecules known as peroxiredoxins (Prdxs): all of these function in concert to detoxify and control the intracellular levels of reactive oxygen species, thus providing cytoprotection by maintenance of survival signaling. GSTπ = glutathione S-transferase π, TRX = thioredoxin, TRXR = thioredoxin reductase, GSH = glutathione (reduced), and GSSG = glutathione (oxidized), Cys_p-SH = reduced peroxidatic cysteine, Cys_p-SOH = oxidized peroxidatic cysteine (sulfenic acid).

Fig. 3.

Possible reaction pathways for spontaneous isomerization of aspartic acid (Asp) and deamidation of asparagine (Asn) residues in protein. The simultaneous formation of β- and d-Asp residues in the protein could be explained in the following four steps. (i) When the carbonyl group of the side chain of the lα-aspartyl residue/lα-Asn is attacked by the nitrogen of the amino acid residue following the Asp residue, l-succinimide is formed by intramolecular cyclization. (ii) l-succinimide may be converted to d-succinimide through an intermediate [I] that has the prochiral α-carbon in the plane of the ring. (iii) Protonation of the intermediate [I] may proceed from the upper or lower side of the plane in an ordinary peptide or protein. (iv) d- and l-succinimide are hydrolyzed at either side of their two carbonyl groups, yielding both β- and α-Asp residues, respectively. Thus, four isomers, lα-Asp, lβ-Asp, dα-Asp and dβ-Asp, are simultaneously formed in the protein.

Fig. 4.

The mathematical phantom used to simulate the dose with the Monte Carlo method. The lens was added into the generally used MIRD phantom. The dose posed by any direction of X-ray beam to any position and size can be calculated for dose optimization purposes.

Fig. 5.

The spatial dose distribution simulated with the Monte Carlo method for interventional procedures. Horizontal (X-Y) or vertical (X-Z or Y-Z) dose distributions are shown based on the spatial dose distribution posed by irradiation from the postero–anterior (PA) position, the 30° right anterior oblique (RAO) position, or the 45° left anterior oblique (LAO) position. Pink colored areas indicate various stuffs placed in the room (e.g. X-ray equipment, other medical equipments and shelves).

Fig. 6.

Hypothetical mechanisms of radiogenic CVD. Solid arrows represent the inflammation theory. Dashed arrows represent hypotheses discussed here.