The Internet's role in a biodosimetric response to a radiation mass casualty event.

Response to a large-scale radiological incident could require timely medical interventions to minimize radiation casualties. Proper medical care requires knowing the victim's radiation dose. When physical dosimetry is absent, radiation-specific chromosome aberration analysis can serve to estimate the absorbed dose in order to assist physicians in the medical management of radiation injuries. A mock exercise scenario was presented to six participating biodosimetry laboratories as one individual acutely exposed to Co under conditions suggesting whole-body exposure. The individual was not wearing a dosimeter and within 2-3 h of the incident began vomiting. The individual also had other medical symptoms indicating likelihood of a significant dose. Physicians managing the patient requested a dose estimate in order to develop a treatment plan. Participating laboratories in North and South America, Europe, and Asia were asked to evaluate more than 800 electronic images of metaphase cells from the patient to determine the dicentric yield and calculate a dose estimate with 95% confidence limits. All participants were blind to the physical dose until after submitting their estimates based on the dicentric chromosome assay (DCA). The exercise was successful since the mean biological dose estimate was 1.89 Gy whereas the actual physical dose was 2 Gy. This is well within the requirements for guidance of medical management. The exercise demonstrated that the most labor-intensive step in the entire process (visual evaluation of images) can be accelerated by taking advantage of world-wide expertise available on the Internet.

Interlaboratory variation in scoring dicentric chromosomes in a case of partial-body x-ray exposure: implications for biodosimetry networking and cytogenetic "triage mode" scoring.

The international radiation biodosimetry community has recently been engaged in activities focused on establishing cooperative networks for biodosimetric triage for radiation emergency scenarios involving mass casualties. To this end, there have been several recent publications in the literature regarding the potential for shared scoring in such an accident or incident. We present details from a medical irradiation case where two independently validated laboratories found very different yields of dicentric chromosome aberrations. The potential reasons for this disparity are discussed, and the actual reason is identified as being the partial-body nature of the radiation exposure combined with differing criteria for metaphase selection. In the context of the recent networking activity, this report is intended to highlight the fact that shared scoring may produce inconsistencies and that further validation of the scoring protocols and experimental techniques may be required before the networks are prepared to deal satisfactorily with a radiological or nuclear emergency. Also, the findings presented here clearly demonstrate the limitations of the dicentric assay for estimating radiation doses after partial-body exposures and bring into question the usefulness of rapid "triage mode" scoring in such exposure scenarios.

Comparison of internal dose measures of solvents in breath, blood and urine and genotoxic changes in aircraft maintenance personnel.

Solvents and fuels are in widespread use both in civilian and military populations. 1,1,1-trichloroethane (TCA), xylene, toluene, methyl ethyl ketone (MEK) and methylene chloride are found in a variety of compounds including degreasing agents, paints, coatings, pesticides and paint strippers. Toluene and xylene are also found in fuels, which are complex mixtures of hundreds of agents. The purpose of this investigation was twofold. The first was to determine the optimum medium to measure internal dose of solvents comparing blood, urine and breath. The second was to determine if low level exposures were associated with genotoxic changes after a short-term exposure of fifteen or thirty weeks. To accomplish the first goal a pilot study was initiated involving eight volunteers who worked in aircraft maintenance including sheet metal, painting and assembly mechanic jobs. Industrial hygiene measurements were evaluated over 30 working days. Breath, blood and a 24-hour urine sample were collected twice to compare internal dose parameters. To achieve the second goal, 58 newly hired subjects were monitored prior to exposure and over 30 weeks to determine if there were genotoxic changes as a result of solvent and/or fuel exposure as measured by sister chromatid exchanges (SCEs) and micronuclei (MN). Exposure groups included workers involved in sheet metal (fuel cell) activities, painting, fueling operations and flight line. Results of the pilot study demonstrated that industrial hygiene air samples and internal breath measures taken on the same day were highly correlated for measuring TCA (r = 0.93) and toluene (r = 0.90) but was not as well correlated for the other compounds. Breath measures were more sensitive for measuring low level exposure than were either analytes in blood or 24-hour urine samples; these latter two measures were usually below the limit of detection. A small but statistically significant increase in the frequency of SCEs occurred after 30 weeks of exposure for sheet metal workers (p = 0.003) and for painters (p = 0.05). The MN frequency in the sheet metal workers initially showed a significant increase by 15 weeks, but by 30 weeks had decreased. Chance occurrence of exposures to other occupational or non-occupational agents can not be eliminated as a cause of the genotoxic results since between 58 and 93 total analytes could be found in the breath of some aircraft maintenance personnel.

Structural and numerical chromosomal aberrations in a metabolically competent human lymphoblast cell line (MCL-5).

MCL-5 cells are Epstein Barr virus-transformed human lymphoblasts which have been genetically engineered for use in mutagenicity testing. We have examined the modal chromosome number, karyotype and spontaneous micronucleus (MN) and sister chromatid exchange (SCE) frequencies of the cell line. Replicate experiments were conducted on two different shipments purchased from Gentest Corp. Although the modal chromosome number was 48 (range 40-54, n = 400 metaphases) for both cell shipments, the second stock showed greater variation in chromosome number than the first. A total of 60 G-banded metaphase cells was analyzed and seven karyotypes were prepared. Consistent structural abnormalities (translocations, deletions and isochromosomes) were found involving the X chromosome and seven autosomes (1-3, 5, 6, 9 and 11). The karyotype typical of this cell line was: 48,der(X)t(X;?)(p22.3;?)Y,t(1;2)(q23;p23),del(3)(q12q21), + i(3q),t(5;6) (q31;p23),+i(9p),der(11)t(11;13)(q23;q12). The mean MN frequency was 41.8 MN/1000 binucleate cells (n = 5000). When compared with our historical controls for primary lymphocyte cultures this number (41.8) is significantly (8.4-fold) higher. The mean SCE frequency was 7.3 per metaphase (n = 100). We observed a hyperdiploid chromosome number of 48 in the majority of metaphase spreads, indicating a significant deviation from the normal diploid number characteristic of the parent cells (RPMI 1788) established in 1969. The variation in chromosome number distribution observed between shipments suggests the potential for further changes. The elevated MN frequency suggests that evaluating mutagenicity using this cytogenetic end-point may require excessive dosing to produce a significant response over background. We conclude that careful interpretation of cytogenetic end-points is necessary when using MCL-5 cells in the light of the possibility of clonal evolution presented here.

Genotoxic changes after low-level solvent and fuel exposure on aircraft maintenance personnel.

Individuals may be exposed to solvent mixtures and fuel either at work or home, through air, water and food contamination. Few studies have addressed the genotoxic effects of mixed, low-level exposure to fuel and solvent. This was an optimally designed study where each subject was sampled prior to exposure and after 15 and 30 weeks while exposed, in a repeated measures design with each subject serving as his own control. Fifty men aged between 18 and 50, working on aircraft equipment operation and maintenance at a military installation were included. Eight unexposed men were concurrently sampled. Sister-chromatid exchanges (SCE) and micronuclei (MN) frequency were measured in conjunction with air sampling and expired breath analysis for jet fuel (JP-4), 1,1,1-trichloroethane, methyl ethyl ketone, xylenes, toluene and methylene chloride. Exposure levels measured by industrial hygiene were very low (all means <6 p.p.m.), <10% of the OSHA standard. Expired breath levels were also low, <25 p.p.b. A small but statistically significant increase in the frequency of SCE occurred after 30 weeks of exposure for sheet metal workers (P = 0.003) and for painters (P = 0.05). The MN frequency in the sheet metal workers initially showed a statistically significant increase, but by 30 weeks had decreased. Cigarette smoking, alcohol and caffeine use were not associated with changes from baseline for either MN or SCE. Smokers, however, had significantly higher values of SCEs at baseline than did nonsmokers. In summary, these findings suggest that small increases in SCEs in particular, may serve as a sensitive biologic indicator of low level hydrocarbon exposure in as much as statistically significant changes occurred in the highest exposed groups but not in the low or no exposure groups. Chance occurrence or exposures to other occupational or non-occupational agents cannot be eliminated as a cause of the study findings.

O6-alkylguanine DNA alkyltransferase activity in student embalmers.

O6-Alkylguanine-DNA alkyltransferase (AGT) activity was assessed in peripheral blood lymphocytes among 23 mortuary science students before and after 9 weeks in a laboratory course in techniques of embalming. Formaldehyde exposure was established by environmental monitoring. The average air concentration of formaldehyde during embalming was about 1.5 ppm. At the pre-exposure sampling, baseline DNA repair capacity tended to be reduced in subjects who reported a prior history of embalming (p = 0.08). From pre- to post-exposure, 17 subjects decreased in DNA repair capacity, while only 6 increased (p < 0.05). Analysis of variance, including adjustment for age, sex, and smoking status, confirmed these findings. Among the eight subjects who had no embalming experience during the 90 days before study, seven had decreased and one had increased AGT activity during the period of study (p < 0.05). For those with prior embalming experience, 10 subjects decreased in AGT activity, while 5 increased (p < 0.05). Although the major chemical exposure in embalming practice was to formaldehyde, no clear link was established between amount of formaldehyde exposure and AGT activity.

Radiobiological evaluation of immigrants from the vicinity of Chernobyl.

Eighty individuals (55 adults and 25 children) who were residents of four cities (Kiev, Mozyr, Gomel and Bobrujsk) located 100-200 km from Chernobyl at the time of the accident in 1986 were tested after immigrating to the US from 1989-1991. A whole-body counter was employed to quantitate radiocesium content. In addition, two biological measures of radiation effects, namely, chromosomal integrity using the micronucleus assay and somatic mutation analysis of erythrocytes at the glycophorin A (GPA) locus, were applied to this group. Radiocesium activity in the body ranged from 0 to 56.8 Bq/kg with a mean and standard deviation of 5.0 +/- 8.2 and a median value of 2.0 Bq/kg. Mean radiocesium content by groups was highest in adult males (9.0 +/- 11.7; range 0.21-56.8 Bq/kg) followed by adult females (3.3 +/- 4.5; range 0-21.3 Bq/kg), male children (3.0 +/- 5.7; range 0-20.2 Bq/kg) and lowest in female children (1.6 +/- 3.5; range 0-12.7 Bq/kg). Individuals with the highest radiocesium content in each group belonged to one family that lived in Mozyr (100 km from Chernobyl) until emigrating in 1989. The frequency of lymphocyte micronuclei and erythrocyte GPA allele-loss (O/N) somatic mutations were both significantly correlated with radiocesium content (r=0.57, p=0.002; r=0.75, p=0.002, respectively). The micronucleus frequency also correlated with the estimated internal absorbed dose from radiocesium in a subset of 20 immigrants for whom this calculation was possible (r=0.71, p=0.0005). Altogether, the biomonitoring data indicate that some subjects had radiation doses sufficient to produce gene and chromosomal mutations in blood cells, although these effects cannot be attributed solely to radiocesium exposure.

Induction of micronuclei and sister chromatid exchanges by polycyclic and N-heterocyclic aromatic hydrocarbons in cultured human lymphocytes.

Many natural environments are contaminated with carcinogenic polycyclic aromatic hydrocarbons (PAHs) and N-heterocyclic aromatic hydrocarbons (NHAs) as complex mixtures of coal tar, petroleum, and shale oil. These potentially hazardous substances are prevalent at many former tar production and coal gasification sites. Three polycyclic [benzo(a)pyrene (BaP), benz(a)anthracene (BAA), and 7,12-dimethylbenz(a)anthracene (DMBA)] and two N-heterocyclic [7H-dibenzo(c,g)carbazole (DBC), and dibenz(a,j)acridine (DBA)] aromatic hydrocarbons were analyzed for cytotoxic and genotoxic effects on human lymphocytes. All of these polyaromatic compounds are normally present in the environment, except for DMBA. Lymphocytes from healthy donors were isolated from whole blood. The 5-ring polycyclic aromatic BaP consistently induced micronuclei in a linear dose-dependent manner with doses from 0.1-10.0 micrograms/ml, whereas the 4-ring compounds (BAA and DMBA) had no effect on the induction of micronuclei above controls except at 5 and 10 micrograms/ml. Of the two N-heterocyclic compounds, DBC produced a significant increase in micronuclei in lymphocytes, but the dose response tended to plateau above 0.1 microgram/ml. DBA showed an effect on the frequency of micronuclei above controls only at high doses of 5 and 10 micrograms/ml. The average background frequency of micronuclei for 7 lymphocyte donors averaged 3.1 per 1,000 stimulated cells, whereas the average frequency of micronuclei at 10 micrograms/ml BaP was 36.8 per 1,000 stimulated cells. The lowest effective dose in 2 donors for BaP occurred at 0.1 microgram/ml. At a challenge dose of 1 microgram/ml (4 microM) of BaP, considerable variation in micronuclei induction between 7 individuals was observed, ranging from 2-6-fold increases above spontaneous frequency. Over a dose range of 1-10.0 micrograms/ml (4-40 microM), BaP also induced sister chromatid exchanges (SCEs) in lymphocytes, whereas BAA had no effect above controls. Parallel studies of both cytogenetic endpoints showed that the micronucleus assay is a more sensitive indicator of BaP exposure at equivalent doses. Mitotic and replication indices of BaP-exposed lymphocytes showed that cell proliferation is only moderately inhibited even at the highest dose; this shows that bulky DNA-adducts are generally compatible with cell survival. The cytogenetic data are consistent, first-off, with reports that individuals in the population vary widely with respect to the inducibility of the CYP1A1 gene, which is known to be involved in polycyclic aromatic hydrocarbon metabolism, in particular, in BaP. Secondly, the data support the fact that polyaromatic compounds differ with regard to micronucleus induction within the same sample(s) of human lymphocytes, indicating selective metabolism of polyaromatic compounds that may reflect carcinogen sensitivity of the individual.(ABSTRACT TRUNCATED AT 400 WORDS)

Sources of variability in the human lymphocyte micronucleus assay: a population-based study.

The cytokinesis block method was used to examine the intraclass correlation coefficient of the human lymphocyte micronucleus assay, sources of variability, and practical issues regarding the number of samples per subject. Twenty samples of 100 binucleate cells from a single phlebotomy per subject were analyzed (n = 112), using methods to evaluate variance components. The results showed marked intraindividual (sampling error) variation greater than interindividual variation, and no between-group contribution to the total variance. The intraclass correlation was 41.6%, indicating that slightly greater than half of the total variation in micronucleus outcomes was due to error variance (i.e., 58.4%). After adjusting for age, the intraclass correlation coefficient decreased trivially from 41.6% to 39.8%. There was a strong differential gender effect, favoring a greater micronuclei frequency in women. In conclusion, the data suggest that most of the variability in our data set for the micronucleus assay was due to sampling error; a strong differential gender effect favoring females was also verified. Equally important, in terms of practical applications, our analysis of the appropriate number of samples per subject revealed that scoring greater than 1,000 cells (10 determinations per subject) yielded no substantial improvement in statistical sensitivity, compared to the traditional 20 determinations. We suggest that more attention should be directed toward improving the assay's utility, while reducing sampling error.

Effect of in vivo exposure to iodine-131 on the frequency and persistence of micronuclei in human lymphocytes.

The validity of the micronucleus test as a biomarker of chromosome damage in dividing mammalian cells is well established. This assay was used to study the response of peripheral lymphocytes of a 34-yr-old male patient following treatment with 131I ablative radiation therapy following a total thyroidectomy. Coincidentally, 8 mo before diagnosis, the patient had provided a blood sample for an in vitro study of micronucleus induction following exposure to graded doses of x-rays. The background frequency in the unexposed culture showed a mean count of 6.0 micronuclei per 1000 binucleated (first division) lymphocytes, while mean values of 18.5, 29.0, 41.0, 61.0 and 75.5 micronuclei/1000 cells were observed following x-ray doses of 5, 10, 15, 20, and 25 cGy, respectively. These data fit a nonthreshold, linear dose-response function (y = 2.78x + 3.71; r = .99). Eight months after the in vitro x-ray study, the subject was diagnosed with thyroid cancer. Surgery was performed, and 5 wk later the patient received 1.78 GBq (48 mCi) of 131I as adjuvant radiation therapy. Blood was drawn 11 d after the radiation treatment and at monthly intervals thereafter to analyze the frequency and persistence of micronuclei. The first posttreatment sample showed 35.5 micronuclei per 1000 binucleate cells. Based on the linear dose-response equation from the earlier study, the sixfold increase in micronucleus frequency suggests a dose to the peripheral blood of approximately 11 cGy. The cytogenetic dose estimate compares to approximately 30 cGy using a new model based on external whole-body counting data. Nine consecutive monthly samples have been analyzed to date. Although the micronucleus count has fluctuated (four- to sixfold above background), the frequency after 8 mo is equivalent to the first posttreatment sample. Data show that radiation-induced cellular lesions persist for months following relatively brief radiation exposure to a medical isotope. Results of this study support the conclusion that the lymphocyte micronucleus test is a rapid, sensitive, and perhaps quantitative biomarker of low-dose (< 25 cGy) radiation exposure.

Cytogenetic effects of formaldehyde exposure in students of mortuary science.

The effect of low-level exposure to formaldehyde on oral, nasal, and lymphoycte biological markers was studied prospectively in a group of 29 mortician students who were about to take a course in embalming. During the 85-day study period, the subjects performed an average of 6.9 embalmings and had average cumulative formaldehyde exposures of 14.8 ppm-h, with an average air concentration of 1.4 ppm during embalming. Since the average time spent embalming was 125 min, formaldehyde exposures calculated as an 8-h time-weighted average were 0.33 ppm on days when embalmings were done, which was less than the Occupational Safety and Health Administration permissible exposure limit of 0.75 ppm. Epithelial cells from the buccal area of the mouth showed a 12-fold increase in micronucleus frequency during the study period, from 0.046 +/- 0.17/1000 cells preexposure to 0.60 +/- 1.27/1000 cells at the end of the course (P < 0.05). Nasal epithelial micronuclei increased 22%, from 0.41 +/- 0.52/1000 cells to 0.50 +/- 0.67/1000 cells (P = 0.26). In blood cells, the frequency of micronucleated lymphocytes increased 28%, from 4.95 +/- 1.72/1000 cells to 6.36 +/- 2.03/1000 cells (P < 0.05), while sister chromatid exchanges decreased 7.5% (P < 0.05). A dose-response relationship was observed between cumulative exposure to formaldehyde and increases in buccal micronuclei in the 22 male subjects but not in the 7 female subjects. We conclude that low-level exposure to formaldehyde is associated with cytogenetic changes in epithelial cells of the mouth and in blood lymphocytes. These cytogenetic effects may be useful as markers of biologically effective dose.

In vitro micronucleus bioassay of human peripheral lymphocytes for adriamycin in the presence of cyclophosphamide and urines of patients administered anticancer drugs.

The aim of this study was to develop an in vitro human peripheral lymphocyte micronucleus bioassay involving phytohemagglutinin stimulant for urines containing adriamycin (ADR) and cyclophosphamide (CP). In vitro studies with defined concentrations of ADR, CP, and fresh urine showed that mitotic indices and micronuclei counts/1,000 cells had to be log (X + 1) transformed to be able to use parametric statistics and that a specific micronucleus assay for ADR in the presence of CP and urine for 5-15 ng ADR/mL had been developed. Whereas CP alone could be detected between 196-522 micrograms/mL, this effect was abolished in the presence of 15 ng ADR/mL. Interdonor variabilities relative to ADR sensitivity and CP linear dynamic range were marked, but intradonor variability was small. The MN bioassay tolerated < 10% urine. Results for urines from nine patients receiving antineoplastic drugs (CP, all; ADR, 3; 5-fluorouracil, 3; methotrexate, 3; vincristine, 4; procarbazine, 1; and megestrol acetate, 1) showed that only 1/3 patients given ADR were detected, and two others not given ADR were positive. All frozen urines from the 12 control subjects and the nine patients exhibited depressed mitotic index, with, however, no control patient urines inducing increased micronuclei. Two patients had urines of undefined genotoxic potential since undepressed mitotic indices were not attainable by dilution. The effects of combination chemotherapy in addition to freezing and storage influences were complex. More research is required to be able to interpret the results.

Reproductive integrity of mammalian cells exposed to power frequency electromagnetic fields.

Human lymphocytes and Chinese hamster ovary (CHO) fibroblasts were analyzed for cytogenetic and cytotoxic endpoints to determine whether exposure to power frequency (60 Hz) electromagnetic fields (EMF) interferes with normal cell growth and reproduction. An exposure chamber was built to apply variable electric current densities of 3, 30, 300, and 3,000 microA/cm2, simultaneously with a fixed magnetic field of 2.2 G to proliferating cells. The current densities were chosen to bracket those that may be induced in the human body by fields measured beneath high voltage (765 kV) power transmission lines. The electric current was applied through the media of a cell culture chamber positioned between two stainless steel electrodes but separated from direct contact with the culture media by a salt bridge composed of a 1% agarose gel. The magnetic field was generated using two pairs of Helmholtz coils driven 73 degrees out of phase producing an elliptically polarized magnetic field 36 degrees out of phase with the electric field. The EMFs were measured and mapped inside the cell culture chamber to insure their uniformity. CHO cells were exposed continuously for 24-96 hr (depending on experiment) and human lymphocytes were exposed continuously for 72 hr. The EMFs were monitored throughout the entire treatment period using a multichannel chart recorder to verify continuous application of the desired fields. Sister-chromatid exchange and micronuclei were monitored to evaluate the potential for genotoxicity. In addition, standard growth curves, clonogenicity, and cell cycle kinetics were analyzed to evaluate possible cytotoxic effects. The experimental data consistently showed that the growth rate and reproductive integrity of both cell types was unaffected by exposure to the electromagnetic fields.

Induction of nuclear aberrations by smokeless tobacco in epithelial cells of human oral mucosa.

Cytologic and cytogenetic studies were performed to assess the prevalence of somatic cell genetic damage in 48 young adults equally divided to represent users and nonusers of smokeless tobacco. Exposure was ascertained by measuring saliva cotinine using capillary gas chromatography. Squamous epithelial cells sampled from the oral mucosa demonstrated significant cytologic alterations associated with tobacco exposure. The frequency of micronucleated cells was significantly (P less than .01) higher in the labial mucosa of exposed (2.22%) compared to unexposed (0.27%) individuals. The frequency of micronuclei varied widely between exposed subjects but was higher in heavily (2.48%) compared to lightly (1.29%) exposed individuals as measured by saliva cotinine levels. Morphologic classification of epithelial cell nuclei showed that the frequency of cells with normal nuclear structure was significantly (P less than .01) reduce in exposed individuals. Analysis of oral epithelial cells of five additional nonusers of smokeless tobacco but wearers of orthodontic appliances to stimulate abrasion demonstrated no difference from the nonexposed control group. Unlike the case with cigarette smokers, peripheral lymphocyte sister-chromatid exchange frequency was not affected by exposure to smokeless tobacco. The oral cytology data, however, support an interpretation of exposure-dependent nuclear alterations, including micronuclei, in the oral epithelium associated with the use of smokeless tobacco. Altogether, results suggest that use of smokeless tobacco may cause genetic damage to cells in the oral epithelium.

Progressive systemic sclerosis associated with exposure to trichloroethylene.

Trichloroethylene (CHCL = CCL2) is a colorless aliphatic organic solvent with both historical use in medicine as an anesthetic agent and current use in industry as a degreasing agent. Although neither the etiology nor pathogenesis of progressive systemic sclerosis (scleroderma) has been established, this disease has been associated with a wide variety of seemingly unrelated compounds, including exposure to organic solvents. The authors describe a 47-year-old woman with previous excellent health who developed fatal progressive systemic sclerosis after a single 2.5-hour predominantly dermal exposure to trichloroethylene. During a period of 10 months the patient developed proximal scleroderma, reflux esophagitis, microangiopathic hemolytic anemia, restrictive pulmonary disease, pericarditis with effusion, and renal insufficiency with severe hypertension. Renal and skin biopsies were consistent with progressive systemic sclerosis.

An unstable giant satellite associated with chromosomes 21 and 22 in the same individual.

The short arms of the acrocentric chromosomes are among the most common sites in which to find human chromosomal heteromorphisms. Heteromorphic chromosomes are noted for their variability between individuals and populations; however, they generally are consistent within an individual. Contrary to this general rule, a normal female was found to have a giant satellite on the short arm of a chromosome 22 in most lymphocytes and fibroblasts, but in other cells, it was attached to a chromosome 21. Furthermore, in some cells, it was found on multiple chromosomes, that is, on both 22's or on a 21 and a 22. The familial nature of this heteromorphism was established when it was found in the woman's mother, where it was confined exclusively to chromosome 22. These results suggest an unstable giant satellite associated with both G-group chromosomes of a normal individual. Results are discussed in the light of the patient's occupational exposure to insecticides at a mushroom farm.

Sister-chromatid exchange frequency in lymphocytes of smoking and nonsmoking mothers and their newborn infants.

Sister-chromatid exchange (SCE) frequency in lymphocytes of 8 smoking mothers and their 9 newborns (one subject bearing twins) was compared to 6 mothers who had never smoked and their 6 newborn infants. Mothers in the first group were required to have smoked throughout pregnancy and to have a minimum of 15 pack-years smoking history. Results confirm our earlier smoking effect reported for adults, deny an effect on the newborn, and concur with other studies that show neonates have consistently lower SCE frequencies than adults. Overall, results are consistent with the idea that toxic substances in tobacco smoke interact with chromosomal DNA of circulating human lymphocytes.

Sister chromatid exchange: variation by age, sex, smoking, and breast cancer status.

Variation in sister chromatid exchange (SCE) frequency in lymphocytes of 125 persons was compared using a multivariate general linear model. The study was performed to determine whether SCE frequency differs with respect to age, sex, smoking, and breast cancer status. Study subjects were divided into: members of two branches of families having an excess of cancer (primarily breast) including a brother and sister in one family who developed nonbreast malignancies within 1 yr of the study; women in both families successfully treated for breast cancer (all at least 5 yr posttreatment); and women from the general population with confirmed breast cancer. Controls consisted of spouses who married into the high-risk kindreds, hospital personnel, and others (primarily tradesmen without history of occupational exposure). Results show that: (1) Women with active breast cancer have a significantly higher mean SCE frequency than control women or women greater than 5 yr posttreatment for breast cancer; (2) Cigarette smokers show a significantly higher number of SCEs than was observed in nonsmokers; (3) The increase in SCE level in smokers is dose-related to exposure as measured by cumulative pack-years; (4) SCE values in both high-risk families are not significantly different from controls; (5) Neither the age nor sex of the individual affects SCE frequency; and (6) The observed distribution of exchanges agrees with that expected based on the proportion of the genome represented by each chromosome group.