New models for prediction of micronuclei formation in nuclear medicine department workers


Application of ionizing radiation in many different fields is constantly increasing,
including the use for medical purposes. Ionizing radiation is known to induce mutations
and cell transformations, predominantly by causing single-strand and double-strand
DNA breakage, thereby leading to chromosome instability and carcinogenesis 10]. Of all workers exposed to man-made sources of radiation, medical personnel represent
the largest group, but receive relatively low doses. However, some medical uses of
radiation, such as nuclear medicine and interventional procedures, may expose personnel
to higher doses, and these are subjects of particular concern 11]. Cytogenetic studies report a significant increase of chromosomal damage in exposed
subjects, especially interventional cardiologists, operational radiologists and nuclear
medicine physicians 12], 13]. On the other hand, some studies concerning mixed population of hospital workers
do not report data on cytotoxicity if the measures of prevention and protection from
radiation were undertaken adequately 14].

Our study established that the incidence of MN significantly increased for health
workers in nuclear medicine departments occupationally exposed to ionizing radiation
in comparison to unexposed individuals. Our findings are in accordance with the most
other literature data 15]–17]. The novelty of this study, that sets it apart from other similar investigations,
is construction of a new model for prediction of micronuclei formation in nuclear
medicine department workers professionally exposed to ionizing radiation. This model
showed that duration of radiation exposure and received annual doses could be used
as predictors of MN frequency. Moreover, the originality of our study lies in the
fact that it has taken into account the potential impact of working place and specific
daily work activities of employees who are in contact with sources of radiation in
nuclear medicine department. Additionally, applying the ROC analysis we have, for
the first time in this study, set the cut of points of TYS, EYS, AD and age that can
imply on higher risk for MN production.

Researchers usually did not find any associations between the MN frequency and the
duration of employment except for interventional cardiologists, where MN values are
higher in physicians with exposure 10 years in comparison with exposed physicians
with hospital work lasting less than 10 years 18]. On the other hand, some authors point out that the length of exposure increases
chromosomal aberrations and the number of damaged cells 19]. Moreover, an increased frequency of bi-nucleated and mono-nucleated cells with micronuclei
was observed in most of the studies, based on the accumulated radiation dose: statistically
significant values were observed above 10 mSv cumulative effective dose along a number
of years of employment 19]. Our findings also indicate that the most important predictors for hospital personnel
working with radiation sources are received annual doses and duration of EYS. Receiving
more than 1.5 mSy annually significantly increases the production and frequency of
MN in workers’ cells. Technicians and laboratory workers are at higher risk for MN
occurrence as they are generally exposed to more radiation than doctors and engineers.

Evidence in the literature shows a significant correlation of MN frequency with older
age and female sex 16], 17]. These findings were confirmed by the results of our study, as well. Women had more
MN in the overall population, but among the exposed personal, there were no significant
differences regarding MN numbers. Persons occupationally exposed to radiation typically
have less than 10 micronuclei if they were exposed for less than 5 years. This all
might indicate that radiation itself is more important than workers sex. We also found
that, in our population, nuclear medicine department workers aged above 43 years,
with more than 20.5 years of TYS and 14.5 years of EYS have more MN. As all received
doses were within referent limits, our findings might imply that older personnel should
be in some way shielded from adverse effects of radiation more than younger health
workers. Perhaps in the age group above 43 years, referent doses should be lowered,
which might be the possible methods of preventing adverse effects of radiation in
the older population of health workers.

Some studies found that smoking might increase MN numbers in cells of workers exposed
to radiation 16]. Still, the majority of literature data agree that it did not affect the MN frequency
if examinees consumed less than 20 cigarettes per day, while a significant effect
was only registered for heavy smokers 20]. According to our results nicotine use also did not have significant influence on
MN formation.

Finally, our results illustrated that low levels of chronic occupational exposure
to ionizing radiation causes increased frequency of MN in cells, even when the absorbed
dose is below the acceptable limit. Consequently, occupational exposure to radiation
can be determined as a risk factor for genotoxicity. The main predictors of the formation
and the number of MN in cells, according to our results and the model we constructed,
are received annual doses and the length of exposure to ionizing radiation of staff
regardless of their specific workplace. Based on the Poisson model, one EYS year increases
the frequency of MN per 1000 binuclear cells 1.017 times, while receiving 0.1 mSy
raises MN frequency by 26 %. The additional co-factors include age and sex, and they
should be closely involved in genetic research monitoring risk assessment of chronic
exposure to low doses of radiation of health workers employed in the departments of
nuclear medicine. The constructed model might be useful in further research aiming
on lowering the referent doses or determining a cut off value for MN in exposed personnel
for whom a genotoxic risk is too high. Moreover, it could be used in clinical practice
for calculating the number of MN in health workers in case that blood analyses are
unavailable, while clinical parameters are known. The equation can be applied to all
personnel working with ionizing radiation. It was constructed for our population,
but could be used in other countries as well.

MN analysis in human lymphocytes using the cytochalasin B technique has been proposed
as a valid and reliable procedure for the assessment of chromosomal damage induced
by ionizing radiation. The cytokinesis-blocked micronucleus test has the advantage
to detect in interphase both acentric chromosome fragments attributed to DNA breakage
and chromosome loss resulting from chromosome lagging in anaphase 21]. Therefore this method was applied in our study as well. This study also demonstrates
the usefulness of MN analysis for individual risk assessment in programs of medical
surveillance of employees in the departments of nuclear medicine.

This study has some limitations. Although we assessed MN frequency, we did not score
nuclear buds and nucleoplasmic bridges. Knowing that one dicentric chromosome manifests
as one nucleoplasmic bridge, this additional scoring could provide a stronger causation
between IR and potential risk for cancer in occupational settings. However, we are
leaving this as well as assessment of other possible genotoxicities for further research.
Moreover, currently there were not enough patients to make 5-years or 1-year age groups.