MEASUREMENT OF CHROMOSOMAL-ABERRATIONS, SISTER-CHROMATID EXCHANGE, HPRT MUTATIONS, AND DNA-ADDUCTS IN PERIPHERAL LYMPHOCYTES OF HUMAN-POPULATIONS AT INCREASED RISK FOR CANCER

Using a multidisciplinary approach, we have measured various indicator s of DNA damage in peripheral lymphocytes of human populations potenti ally at increased risk for cancer. Sister chromatid exchanges (SCE) an d polycyclic aromatic hydrocarbon (PAH)-DNA adducts were evaluated in a group of firefighters; chromosomal aberrations and hprt mutations we re evaluated in a group of cancer patients undergoing radioimmunoglobu lin therapy (RIT); SCE and acrolein-modified DNA were measured in canc er chemotherapy patients and in pharmacists preparing chemotherapy pre scriptions; and SCE and PAH-DNA adducts are being measured in U.S. arm y troops stationed in Kuwait. Our results indicate that both SCE and P AH-DNA adduct levels were not elevated in firefighters, but that other factors such as smoking status and race were risk factors for increas ed SCE and PAH-DNA adducts. RIT was found to increase background rates of chromosome-type aberrations and frequencies of hprt mutations and there was a strong correlation between levels of therapy-induced chrom osome damage sustained in vivo and in vitro sensitivity to radiation-i nduced chromosome damage. Peripheral blood lymphocytes of cancer patie nts treated with cyclophosphamide showed higher levels of SCE and had a higher incidence of acrolein adducts in DNA. Lymphocytes from pharma cists preparing antineoplastic drugs were found to acquire increased i n vitro sensitivity to SCE induction by phosphoramide mustard with inc reased lifetime duration of drug handling. A prospective, longitudinal study was performed to identify environmental factors that modulate g enetic damage in breast cancer patients. Women with benign breast mass es and no apparent disease served as controls. Mutant frequency, cloni ng efficiency, and chromosomal aberration frequency did not differ sig nificantly among the three groups. The results described and the data being gathered on troops stationed in Kuwait suggest that all the meth odologies described can be useful in screening human populations for m utagenic exposures.