Comparative study on Salmonella mutagenicity and on cytogenetic and antineoplastic effects induced by cyclophosphamide and 3-aminobenzamide in cells of three transplantable tumours in vivo.

Synergistically enhanced sister chromatid exchange (SCE) frequency by cyclophosphamide (CP) was observed when L1210 lymphoid tumor cells were exposed in vivo to a non-toxic concentration of 3-aminobenzamide (3-AB). Additive effects in SCE induction in vivo were observed when either Ehrlich ascites tumor (EAT) cells or P388 lymphocytic leukemia cells treated with CP were exposed to 3-AB in vivo. 3-AB enhanced the survival time of L1210 tumor bearing BDF1 mice treated with CP.

Enhancement of cytogenetic damage and of antineoplastic effect in lymphoid L1210 leukemia cells treated with prostaglandin E2 and cyclophosphamide in vivo.

An enhanced frequency of sister-chromatid exchanges (SCEs) and increased cell division delays induced by cyclophosphamide (CP) were observed when lymphoid L1210 leukemia cells were post-treated in vivo with prostaglandin E2 (PGE2). CP gave a slight, non-significant increase in survival while PGE2 gave a slight, non-significant decrease in survival. However, PGE2 in combination with CP was found to have a non-significant potentiating effect on survival in comparison with mice treated with CP alone.

Enhancement of antineoplastic effect and attenuation of sister chromatid exchanges by prostaglandin E2 in Ehrlich ascites tumour cells treated with cyclophosphamide in vivo.

Reduced sister chromatid exchanges (SCE) frequency in response to cyclophosphamide (CP) was observed when Ehrlich ascites tumour (EAT) cells were exposed in vivo to 2 micrograms/g body weight of prostaglandin E2 (PGE2). 1 h before i.p.

Frequencies of chromosomal aberrations in pesticide sprayers working in plastic green houses.

The frequency of chromosome aberrations was studied in peripheral blood lymphocytes of 29 workers occupationally exposed to a mixture of pesticides and in 14 age- and sex-matched healthy controls. There was a significant increase in chromosome aberrations in sprayers when compared to unexposed persons (2.39% compared to 0.

Enhanced genotoxicity by melphalan and hyperthermia in chronic heroin addicts.

Spontaneous melphalan- (MEL-) and MEL-hyperthermia- (MEL-HYP-) induced sister chromatid exchange (SCE) frequencies have been studied in 12 chronic heroin addicts (HER AD) and in 12 age- and sex-matched healthy controls. The incidence of spontaneous SCEs in lymphocytes from the HER AD was significantly greater (P less than 0.001) than those from the control subjects.

Synergistic induction of cytogenetic damage by the homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenylacetic acid in combination with caffeine in human lymphocytes in vitro and in Ehrlich ascites tumour cells in vivo.

We studied the effects of caffeine alone or in combination with homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenylacetic acid (ASE, NSC 290205) on the frequency of SCEs and lymphocyte proliferation kinetics. Caffeine was found to act synergistically with ASE on the induction of SCEs when the two components were administered in combination. Caffeine was also found to act synergistically with ASE in inducing cell-division delays.

Effects of alkylating antineoplastics alone or in combination with 3-aminobenzamide on genotoxicity, antitumor activity, and NAD levels in human lymphocytes in vitro and on Ehrlich ascites tumor cells in vivo.

Enhanced cytogenetic damage by the homo-aza-steroidal ester of p-bis(2-chloroethyl)-aminophenylacetic acid (ASE) was observed when human lymphocytes in vitro or Ehrlich ascites tumor (EAT) cells in vivo were exposed to nontoxic concentrations of 3-amino-benzamide (3-AB). 3-AB at these concentrations was found to enhance synergistically the cytogenetic damage induced in vivo by cyclophosphamide (CP), a metabolically activated chemotherapeutic, or chlorambucil (CBC) in EAT cells. One hour before i.

Comparative study on cytogenetic effects by diplatinum complexes of the ligands of naphthazarine and squaric acid in human lymphocytes.

The effect of diplatinum complexes of the binucleating ligands of naphthazarine and squaric acid on Sister Chromatid Exchange (SCE) rates and human lymphocyte proliferation kinetics was studied. Squarodicisplatinum complex I, naphthazarindicisplatinum and squarodicisplatinum complex II induce cytotoxic effects as can be deduced from the resulted induction of SCEs and the produced cell division delays. Squarodicisplatinum complex I was found to be on a molar basis the most effective in causing markedly increased SCE rates and cell division delays.

Synergistic induction of cytogenetic damage by alkylating antineoplastics and 5-azacytidine in human lymphocytes.

We studied the effects of the inhibitor of DNA methylation, 5-azacytidine (Aza-C), alone and in combination with three antitumor alkylating agents, on sister chromatid exchanges (SCEs) and lymphocyte proliferation kinetics. Aza-C was found to act synergistically on induction of SCEs when administered in combination with either melphalan (MEL) or chlorambucil (CBC) or cis-platinum-(II)diamine dichloride (cis-Pt). Cell-division delays were consistently observed in cultures treated with each of the antineoplastics when introduced concomitantly with Aza-C, compared with cultures treated with antineoplastics alone.

Enhancement of cytogenetic damage by chlorpromazine in human lymphocytes treated with alkylating antineoplastics and caffeine.

In cultured human lymphocytes chlorpromazine (CPZ) was found to induce cell division delays and to have no effect on sister-chromatid exchanges (SCEs) or on mitotic indices (MIs). CPZ induces cytotoxic effects in combination with caffeine (CAF) and alkylating agents. In combination with CAF it induced cell division delays and suppression of MIs.

Enhancement of cytogenetic damage and of antineoplastic effect by caffeine in Ehrlich ascites tumor cells treated with cyclophosphamide in vivo.

Enhanced cytogenetic damage by cyclophosphamide (CP) was observed when Ehrlich ascites tumor cells were exposed in vivo to nontoxic concentrations of caffeine. One h before i.p.

Induction of cytogenetic damage by modified steroidal derivatives of p-bis(2-chloroethyl)aminophenylacetic acid in human lymphocytes.

The effect of modified steroids, containing alkylating agents, on SCE rates and on cell kinetics in cultured human lymphocytes was studied. The homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenylacetic acid (ASE) was found to be the most effective in causing markedly increased SCE rates and cell division delays. The androsterone ester of p-bis(2-chloroethyl)aminophenylacetic acid (AE-CAPA) was found to be next in order of effectiveness with the lactone ester (LE-CAPA), chlorambucil ester 3 beta-hydroxy-13a-amino-13,17-seco-5a-androstan-17-oic-13,17-lactam (CBC-HAAL) and chlorambucil (CBC) following.

Enhancement and attenuation of cytogenetic damage by vitamin C in cultured human lymphocytes exposed to thiotepa or L-ethionine.

Vitamin C (vit C) at 2 mM enhanced sister chromatid exchange (SCE) frequencies induced by Thiotepa (THIO) or L-ethionine (L-ETH) in cultured human lymphocytes. However, when vit C was tested at 0.02 mM and 0.

Induction of sister-chromatid exchanges in heroin-cannabis, heroin and cannabis addicts.

The aim of this study was to determine the frequency of sister-chromatid exchanges (SCEs) in heroin-cannabis, heroin and cannabis addicts. The group of 84 subjects consisted of 42 controls, 16 heroin-cannabis addicts, 12 heroin addicts and 14 cannabis addicts. The mean number of SCEs/cell was 12.

Enhancement of cytogenetic damage by inhibitors of poly(ADP-ribose)polymerase in human lymphocytes exposed to antineoplastics in vivo and in vitro.

The effect of benzamide (B) and 3-aminobenzamide (3-AB) on sister chromatid exchanges (SCEs) and cell kinetics induced in vitro by melphalan (MELPH) or thiotepa (THIO) was studied in normal human lymphocytes. The combined treatments with either MELPH or THIO plus B or 3-AB showed the potentiating ability on SCE rates and the ability to induce cell division delays of the latter chemicals. In a combined in vivo and in vitro study, lymphocytes taken from six cancer patients who had been given cytoxan by injection 2 hr before and then treated with theophylline (THEOPH) or B or 3-AB in vitro were found to have synergistically increased exchange rates and cell division delays.

Induction of sister-chromatid exchanges and cell-cycle delays in human lymphocytes by vitamin A alone or in combination with melphalan and caffeine.

In cultured human lymphocytes vitamin A was found to increase SCE rates, to reduce the mitotic index and to have no effect on cell kinetics. Vitamin A induces cytotoxic effects: in combination with melphalan (MELPH), as can be deduced from the resulted synergism on induction of SCEs, the produced cell division delay and the suppressed mitotic index; in combination with caffeine (CAF), producing synergism on induction of SCEs and suppressing the mitotic index; and in combination with MELPH and CAF, producing cell-cycle delays and reducing the mitotic index.

Synergistic induction of sister-chromatid exchanges in lymphocytes from normal subjects and from patients under cytostatic therapy by inhibitors of poly(ADP-ribose)polymerase and antitumour agents.

The effects of nicotinamide on SCE rates induced in vitro by chlorambucil (CBC or melphalan (MELPH) or mitomycin C (MMC) was studied. The combined treatments with either CBC or MELPH or MMC and nicotinamide showed the potentiating ability of the latter drug. Theophylline and MELPH were also found to act synergistically on the induction of SCEs.

Prostaglandins act synergistically with antitumour agents on induction of sister chromatid exchanges in human lymphocytes.

Prostaglandins (PGs) E1 and E2 were found to enhance Sister Chromatid Exchange (SCE) frequencies induced by Mitomycin C (MMC) or Melphalan (ME-LPH) in cultured normal human lymphocytes. PG E1, E2 and F2a alone had no effect on SCE induction up to the higher concentration tested of 2 micrograms/ml. PG F2a does not act synergistically with MELPH on induction of SCEs.

Practical applications of the SCE studies for guiding and improving chemotherapy.

The effect of diphylline (DP) or (1,2-dihydroxy-3-propyl)-theophylline and theobromine (TB) on sister chromatid exchange (SCE) rates induced in vitro by cytosine arabinoside (AraC) was studied in normal human lymphocytes. The combined treatments with AraC plus DP or TB showed the potentiating ability of the latter drugs. In a combined in vivo and in vitro study, lymphocytes taken from 14 patients suffering from various types of cancer who had been given Cytoxan (5 patients) or AraC (9 patients) by injection 3 hr before and then treated with DP or TB in vitro were found to have synergistically increased exchange rates.

Induction of sister-chromatid exchange in human lymphocytes by vitamin B6.

Vitamin B6, or pyridoxine hydrochloride, enhanced sister-chromatid exchange (SCE) rates in cultured normal human lymphocytes. No increase was found in SCE frequency when lymphocytes were treated with pyridoxal-5-phosphate (P-5-P) or 4-pyridoxic acid (4-PA) to which vitamin B6 is finally converted.

Enhancement by methylxanthines of sister-chromatid exchange frequency induced by cytostatics in normal and leukemic human lymphocytes.

The effect of theobromine (TB) and diphylline (DP) or (1,2-dihydroxy-3-propyl)theophylline on SCE rates induced in vitro by mitomycin C (MMC), and the effect of caffeine on SCE rates induced in vitro by cytosine arabinoside (Ara-C) was studied. The combined treatments with MMC plus TB or DP showed the potentiating ability of the latter drugs. Caffeine also enhanced SCEs induced by Ara-C in cultured human lymphocytes.

Studies in vitro on the effect of adenosine, adenine and NAD on guinea pig myometrium in the presence of exogenously applied PGE2.

In guinea pig isolated uterine strips, separate addition of adenosine, adenine and NAD was without any effect. Adenosine and NAD when administered after previously applied subthreshold dose of PGE2 exhibited a strong contractile effect. Indomethacin, added to the organ bath before addition of prostaglandin, blocked, partially or totally, the observed synergistic action of PGE2 with adenosine and NAD.

The effect of PGE2 and PGF2alpha on the response of guinea pig myometrium to adenine nucleotides in vitro.

Prostaglandins E2 and F2alpha potentiate contractile effect induced by adenine nucleotides ATP, ADP and AMP in guinea pig myometrium in vitro. Prostaglandins and nucleotides were added to the organ bath in minute concentrations which have been proved ineffective or slightly contractile when both groups of substances were administered separately. The data of the present work, together with our previously published studies (9, 10, 13), where the action of exogenous adenine nucleotides, NAD and adenosine on rabbit's jejunum in vitro has been proved antagonistic to the contractile effect of various prostaglandins, suggest that prostaglandins and adenine nucleotides appear to block selectively or augment each other's action on various organs.